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We previously established a thermodynamical model to calculate the specific frequencies of extremely low frequency-electromagnetic field (ELF-EMF) able to arrest the growth of cancer cells. In the present study, for the first time, we investigated the efficacy of this technology on osteosarcoma, and we applied a precise frequency of the electromagnetic field on three human osteosarcoma cell lines, grown as adherent cells and spheroids. We evaluated the antitumour efficacy of irradiation in terms of response to chemotherapeutic treatments, which is usually poor in this type of cancer. Importantly, the results of this novel combinatorial approach revealed that the specific exposure can potentiate the efficacy of several chemotherapeutic drugs, both on bidimensional and tridimensional cancer models. The effectiveness of cisplatinum, methotrexate, ifosfamide and doxorubicin was greatly increased by the concomitant application of the specific ELF-EMF. Moreover, our experiments confirmed that ELF-EMF inhibited the proliferation and modulated the mitochondrial metabolism of all cancer models tested, whereas mesenchymal cells were not affected. The latter finding is extremely valuable, given the importance of preserving the cell reservoir necessary for tissue regeneration after chemotherapy. Altogether, this novel evidence opens new avenues to the clinical applications of ELF-EMF in oncology. [Display omitted] • Our thermodynamic model selects the frequency of ELF-EMF specific for osteosarcoma. • The exposure to ELF-EMF potentiates the efficacy of several chemotherapeutic drugs. • ELF-EMF inhibits growth and modulates mitochondrial metabolism of osteosarcoma. • Mesenchymal cells are not affected by the cancer-specific frequencies of ELF-EMF. • Chemosensitization makes ELF-EMF a promising personalized cancer treatment. [ABSTRACT FROM AUTHOR]

Macrophages play a critical role in the body's defense against cancer by phagocytosing tumor cells, presenting antigens, and activating adaptive T cells. However, macrophages are intrinsically incapable of delivering targeted cancer immunotherapies. Engineered adoptive cell therapy introduces new targeting and antitumor capabilities by modifying macrophages to enhance the innate immune response of cells and improve clinical efficacy. In this study, we developed engineered macrophage cholesterol-AS1411-M1 (CAM1) for cellular immunotherapy. To target macrophages, cholesterol-AS1411 aptamers were anchored to the surface of M1 macrophages to produce CAM1 without genetic modification or cell damage. CAM1 induced significantly higher apoptosis/mortality than unmodified M1 macrophages in murine breast cancer cells. Anchoring AS1411 on the surface of macrophages provided a novel approach to construct engineered macrophages for tumor immunotherapy. [Display omitted] • Engineered M1 macrophages were developed with cholesterol-AS1411 aptamers. • Engineered M1 macrophages maintained their typical properties of M1 macrophages. • This work provided a novel engineered macrophages for tumor immunotherapy. [ABSTRACT FROM AUTHOR]

Cancer remains a leading cause of death, with increasing incidence. Conventional treatments offer limited efficacy and cause significant side effects, hence novel drugs with improved pharmacological properties and safety are required. Silvestrol (SLV) is a flavagline derived from some plants of the Aglaia genus that has shown potent anticancer effects, warranting further study. Despite its efficacy in inhibiting the growth of several types of cancer cells, SLV is characterized by an unfavorable pharmacokinetics that hamper its use as a drug. A consistent research over the recent years has led to develop novel SLV derivatives with comparable pharmacodynamics and an ameliorated pharmacokinetic profile, demonstrating potential applications in the clinical management of cancer. This comprehensive review aims to highlight the most recent data available on SLV and its synthetic derivatives, addressing their pharmacological profile and therapeutic potential in cancer treatment. A systematic literature review of both in vitro and in vivo studies focusing on anticancer effects, pharmacodynamics, and pharmacokinetics of these compounds is presented. Overall, literature data highlight that rationale chemical modifications of SLV are critical for the development of novel drugs with high efficacy on a broad variety of cancers and improved bioavailability in vivo. Nevertheless, SLV analogues need to be further studied to better understand their mechanisms of action, which can be partially different to SLV. Furthermore, clinical research is still required to assess their efficacy in humans and their safety. [Display omitted] [ABSTRACT FROM AUTHOR]

The development of new anticancer agents is one of the most urgent topics in drug discovery. Inhibition of molecular chaperone Hsp90 stands out as an approach that affects various oncogenic proteins in different types of cancer. These proteins rely on Hsp90 to obtain their functional structure, and thus Hsp90 is indirectly involved in the pathophysiology of cancer. However, the most studied ATP-competitive inhibition of Hsp90 at the N-terminal domain has proven to be largely unsuccessful clinically. Therefore, research has shifted towards Hsp90 C-terminal domain (CTD) inhibitors, which are also the focus of this study. Our recent discovery of compound C has provided us with a starting point for exploring the structure-activity relationship and optimising this new class of triazole-based Hsp90 inhibitors. This investigation has ultimately led to a library of 33 analogues of C that have suitable physicochemical properties and several inhibit the growth of different cancer types in the low micromolar range. Inhibition of Hsp90 was confirmed by biophysical and cellular assays and the binding epitopes of selected inhibitors were studied by STD NMR. Furthermore, the most promising Hsp90 CTD inhibitor 5x was shown to induce apoptosis in breast cancer (MCF-7) and Ewing sarcoma (SK-N-MC) cells while inducing cause cell cycle arrest in MCF-7 cells. In MCF-7 cells, it caused a decrease in the levels of ERα and IGF1R, known Hsp90 client proteins. Finally, 5x was tested in zebrafish larvae xenografted with SK-N-MC tumour cells, where it limited tumour growth with no obvious adverse effects on normal zebrafish development. [Display omitted] • A library of new triazoles as Hsp90 C-terminal inhibitors was prepared. • Several compounds inhibited the growth of various cancer cells in vitro. • Binding mode of 5x to Hsp90 was studied by TR-FRET, MST, STD NMR and MD simulations. • 5x decreased the levels of Hsp90 clients in MCF-7 breast cancer cells. • 5x inhibited the growth of Ewing sarcoma in vivo in zebrafish larvae xenografts. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the most common malignant tumors in women and is a serious threat to women's health. The pentose phosphate pathway (PPP) is a mode of oxidative breakdown of glucose that can be divided into oxidative (oxPPP) and non-oxidative (non-oxPPP) stages and is necessary for cell and body survival. However, abnormal activation of PPP often leads to proliferation, migration, invasion, and chemotherapy resistance in breast cancer. Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme in PPP oxidation. Nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) produced by G6PD is the raw material for cholesterol and lipid synthesis and can resist the production of oxygen species (ROS) and reduce oxidative stress damage to tumor cells. Transketolase (TKT) is a key enzyme in non-oxPPP. Ribose 5-phosphate (R5P), produced by TKT, is a raw material for DNA and RNA synthesis, and is essential for tumor cell proliferation and DNA damage repair. In this review, we describe the role and specific mechanism of the PPP and the two most important enzymes of the PPP, G6PD and TKT, in the malignant progression of breast cancer, providing strategies for future clinical treatment of breast cancer and a theoretical basis for breast cancer research. • Targeting G6PD increases ROS levels, and targeting TKT inhibits DNA synthesis, promotes DNA damage, and reduces DNA damage repair capacity. • This review summarizes the role of PPP in breast cancer and the role and mechanism of G6PD and TKT, two of the most important enzymes of PPP, in breast cancer, providing strategies for the treatment and chemotherapy resistance of breast cancer in the future. • We also summarize the signaling pathways and molecular mechanisms involved in the malignant progression of breast cancer by G6PD and TKT, this provides a basis and foundation for future breast cancer and PPP research. [ABSTRACT FROM AUTHOR]

Glinus oppositifolius L., a member of the Molluginaceae family, has a long-standing history of utilization as both a vegetable and a medicinal agent across numerous countries. This plant possesses a diverse range of pharmacological activities and attracts scientific interest in studying its chemical profile. The present phytochemical investigation of the plant resulted in the isolation of eleven new triterpenoid saponins, accompanied by three known compounds. Their structures were elucidated by intensive spectroscopic analysis, DFT calculations, and comparison with previously reported data. The isolates were evaluated for their anti-adipogenic effect and cytotoxicity against human cancer cell lines, namely, colorectal carcinoma HCT116, hepatoblastoma cell HepG2, breast cancer cell MDA-MB-231, and human lung adenocarcinoma cell A549. Compounds 5 , 7 , and 13 exhibited a potent inhibitory effect against the differentiation of preadipocyte 3T3-L1. In addition, compound 13 displayed inhibitory effects against the growth of A549 cancer cells. • Eleven new triterpenoid saponins were isolated from Glinus oppositifolius. • Compounds 5 , 7 , and 13 significantly suppressed adipogenesis in 3T3-L1 cells. • Compounds 13 exhibited moderate inhibition against lung cancer cell A549. • The plant could become a potential source for the development of anti-obesity and anti-cancer therapeutics. [ABSTRACT FROM AUTHOR]

Growth factor-derived peptides are bioactive molecules that play a crucial role in various physiological processes within the human body. Over the years, extensive research has revealed their diverse applications, ranging from antimicrobial properties to their potential in neuroprotection and treating various diseases. These peptides exhibit innate immune responses and have been found to possess potent antimicrobial properties against a wide range of pathogens. Growth factor-derived peptides have demonstrated the ability to promote neuronal survival, prevent cell death, and stimulate neural regeneration. As a result, they hold immense promise in the treatment of various neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis, as well as in the management of traumatic brain injuries. Moreover, growth factor-derived peptides have shown potential for supporting tissue repair and wound healing processes. By enhancing cell proliferation and migration, these peptides contribute to the regeneration of damaged tissues and promote a more efficient healing response. The applications of growth factor-derived peptides extend beyond their therapeutic potential in health; they also have a role in various disease conditions. For example, researchers have explored their influence on cancer cells, where some peptides have demonstrated anti-cancer properties, inhibiting tumor growth and promoting apoptosis in cancer cells. Additionally, their immunomodulatory properties have been investigated for potential applications in autoimmune disorders. Despite the immense promise shown by growth factor-derived peptides, some challenges need to be addressed. Nevertheless, ongoing research and advancements in biotechnology offer promising avenues to overcome these obstacles. The review summarizes the foundational biology of growth factors and the intricate signaling pathways in various physiological processes as well as diseases such as cancer, neurodegenerative disorders, cardiovascular ailments, and metabolic syndromes. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC), a hypervascular tumor, is the most frequent primary malignant tumor of the liver. Angiogenesis inhibitors, such as endogenous angiogenesis inhibitors, are essential for HCC therapy and have generated significant interest owing to their safety, efficacy, and multitargeting attributes. Canstatin is an angiogenesis inhibitor derived from the basement membrane and exerts anti-tumor effects. However, the inhibitory effects and underlying mechanisms of action of canstatin on HCC remain unclear. Therefore, in this study, HepG2 and Huh7 cells were used to investigate the inhibitory effects of recombinant canstatin on HCC cells. Subsequently, the biosafety and inhibitory effects of recombinant canstatin on tumor growth were investigated in a xenograft animal model of liver cancer. Canstatin inhibited the growth of liver cancer cells by regulating their proliferation, apoptosis, and migration. Additionally, it suppressed the occurrence and progression of HCC by modulating the HIF-1α/VEGF signaling pathway. In mice, canstatin exerted no discernible harmful side effects and suppressed the growth of HCC subcutaneous xenograft tumors. Overall, our findings shed light on the molecular pathways underlying canstatin-induced HCC cell death that may help develop novel HCC treatments. [Display omitted] • Recombinant canstatin significantly inhibits the proliferation and migration of HepG2 and Huh7 cells. • Recombinant canstatin inhibits proliferation of HepG2 and Huh7 cells via modulating the HIF-1α/VEGF signaling pathway. • Recombinant canstatin can significantly inhibit the proliferation of Huh7 transplanted tumors in nude mice. [ABSTRACT FROM AUTHOR]

Indoleamine 2,3-dioxygenase 1 (IDO1) is an immune checkpoint that degrades L-tryptophan to kynurenine (Kyn) and enhance immunosuppression, which can be an attractive target for treating colon cancer. IDO1 inhibitors have limited efficacy when used as monotherapies, and their combination approach has been shown to provide synergistic benefits. Many studies have shown that targeting chemokines can promote the efficacy of immune checkpoint inhibitors. Therefore, this study explored the use of IDO1 inhibitors with multiple chemokines to develop a new combination regimen for IDO1 inhibitors. We found that IDO1 inhibitors reduce the secretion of C-X-C motif ligand 10(CXCL10) in cancer cells, and CXCL10 supplementation significantly improved the anticancer effect of IDO1 inhibitors. The combination of the IDO1 inhibitor with CXCL10 or its agonist axitinib had a synergistic inhibitory effect on the growth of colon cancer cells and transplanted CT26 tumors. This synergistic effect may be achieved by inhibiting cancer cell proliferation, promoting cancer cell apoptosis, promoting CD8+T cell differentiation and decreasing Tregs. Two downstream pathways of IDO1 affect CXCL10 secretion. One being the Kyn-aryl hydrocarbon receptor (AHR) pathway, the other is the general control nonderepressible 2(GCN2). Our study provides a new reference for combination regimens of IDO1 inhibitors. [Display omitted] • IDO1 inhibitors reduce CXCL10 secretion in cancer cells, which may impair the anticancer effects of IDO1 inhibitors. • IDO1 inhibitors positively regulate CXCL10 secretion through Kyn-AHR pathway. • GCN2 knockdown promotes IDO1 protein expression and enzyme activity. • IDO1 inhibitors synergize with CXCL10 or its agonists in inhibiting colon cancer growth. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor-engineered T (CAR-T) cell therapy of cancer has been a hotspot and promising. However, due to rapid exhaustion, CAR-T cells are less effective in solid tumors than in hematological ones. CD122+CXCR3+ memory T cells are characterized with longevity, self-renewal and great antitumoral capacity. Thus, it's compelling to induce memory CAR-T cells to enhance their efficacy on solid tumors. Astragalus polysaccharide (APS) has reportedly exhibited antitumoral effects. However, it's unclear if APS has an impact on CD8+ memory T cell generation or persistence. Using two human cancer cell lines, here we found that APS significantly improved the persistence of GPC3-targeted CAR-T cells and enhanced their suppression of tumor growth in both Huh7 and HepG2 xenograft models of hepatocellular carcinoma. APS increased CD122+/CXCR3+ memory T cells, but decreased their PD-1+ subset within CD8+ CAR-T cells in tumor-bearing mice, while these effects of APS were also confirmed with in vitro experiments. Moreover, APS augmented the expression of chemokines CXCL9/CXCL10 by the tumor in vivo and in vitro. It also enhanced the proliferation and chemotaxis/migration of CAR-T cells in vitro. Finally, APS promoted the phosphorylation of STAT5 in CD8+ CAR-T cells, whereas inhibition of STAT5 activation reversed these in vitro effects of APS. Therefore, APS enhanced the antitumoral effects of CD8+ CAR-T cells by promoting formation/persistence of CD122+/CXCR3+/PD-1- memory T cells and their migration to the tumor. [Display omitted] • Astragalus polysaccharide (APS) promotes CD8+ CAR-T cell persistence/proliferation. • APS enhances suppression of hepatocellular cancer growth by CAR-T cells in mice. • It increases frequency of CD122+/CXCR3+/PD-1- subsets within CD8+ CAR-T cells. • It exerts these effects on CD8+ CAR-T cells by enhancing their STAT5 activation. • It also enhances CAR-T cell migration/chemotaxis through CXCR3-CXCL9/10 axis. [ABSTRACT FROM AUTHOR]

Cancers account for many deaths worldwide and natural compounds and their derivatives are interesting chemotherapeutic agents for cancer drug development. In this study, a natural compound 3,3'4-trimethoxy-4'-rutinosylellagic acid (TR2) and its acetylated derivative 3,3'4-trimethoxy-4'-hexaacetylrutinosylellagic acid (TR22) were evaluated for their antioxidant and anticancer effects against estrogen sensitive (MCF-7) and estrogen non-sensitive (MDA-MB 231) breast adenocarcinoma. In the β-Carotene-linoleic acid assay, DPPH• radical scavenging and CUPRAC assay, the compound TR2 had better activity than the standard α-Tocopherol, while in the ABTS•+ assay, it was more active than both standards α- α-Tocopherol and BHA. Both compounds had good antioxidant effects with TR2 being more active than TR22. Both compounds inhibited growth of breast carcinoma cells when compared to the untreated controls after 72 h. Compound TR22 significantly (p < 0.001) inhibited proliferation of both MCF-7 and MDA-MB 231 breast carcinoma cell lines suggesting that acetylation reaction improves inhibition of breast cancer cells growth. On the contrary, TR2 exhibited better inhibitory effect of clone formation than TR22 suggesting that acetylation reduces the activity in this assay. Both compounds inhibited migration of the cancer cells when compared to the untreated control cells and compound TR2 exhibited greater cellular anti-migration effect than TR22 at the same concentration and after the same period of incubation. Molecular docking studies supplemented the results and revealed that TR2 and TR22 had appreciable interactions with tyrosine kinase with negative binding energies suggesting that they are potent receptor tyrosine kinase inhibitors which can impede on cancer progression. • Natural compound 3,3'4-trimethoxy-4'-rutinosylellagic acid was acetylated to 3,3'4-trimethoxy-4'-hexaacetylrutinosylellagic acid. • Both compounds showed in vitro antioxidant properties. • Compounds inhibited proliferation of estrogen sensitive (MCF-7) and estrogen non-sensitive (MDA-MB 231) breast carcinoma. • Compounds reduced clone formation and migration of breast cancer cells. • Negative binding energies suggested appreciable interactions of compounds with tyrosine kinase. [ABSTRACT FROM AUTHOR]

Reprogrammed metabolism is a hallmark of cancer, but notoriously difficult to target due to metabolic plasticity, especially in response to single metabolic interventions. Combining mTOR inhibitor everolimus and mitochondrial complex 1 inhibitor metformin results in metabolic synergy in in vitro models of triple-negative breast cancer. Here, we investigated whether the effect of this drug combination on tumor size is reflected in changes in tumor metabolism using [U-13C]glucose labeling in an MDA-MB-231 triple negative breast cancer xenograft model. The in vitro effects of everolimus and metformin treatment on oxidative phosphorylation and glycolysis reflected changes in 13C-labeling of metabolites in MDA-MB-231 cells. Treatment of MDA-MB-231 xenografts in SCID/Beige mice with everolimus resulted in slower tumor growth and reduced tumor size and tumor viability by 35%. Metformin treatment moderately inhibited tumor growth but did not enhance everolimus-induced effects. High serum levels of everolimus were reached, whereas levels of metformin were relatively low. Everolimus decreased TCA cycle metabolite labeling and inhibited pyruvate carboxylase activity. Metformin only caused a mild reduction in glycolytic metabolite labeling and did not affect pyruvate carboxylase activity or TCA cycle metabolite labeling. In conclusion, treatment with everolimus, but not metformin, decreased tumor size and viability. Furthermore, the efficacy of everolimus was reflected in reduced 13C-labeling of TCA cycle intermediates and reduced pyruvate carboxylase activity. By using in-depth analysis of drug-induced changes in glucose metabolism in combination with measurement of drug levels in tumor and plasma, effects of metabolically targeted drugs can be explained, and novel targets can be identified. [Display omitted] • Everolimus reduces pyruvate carboxylase activity in breast cancer • Metabolic activity in vitro differs greatly from that in vivo • Synergy between metformin and everolimus is absent in vivo • Metformin and everolimus serum and tumor levels explain in vivo effects [ABSTRACT FROM AUTHOR]

Protein disulfide isomerase A3 (PDIA3) promotes the correct folding of newly synthesized glycoproteins in the endoplasmic reticulum. PDIA3 is overexpressed in most tumors, and it may become a biomarker of cancer prognosis and immunotherapy. Our study aims to detect the expression level of PDIA3 in gastric cancer (GC) and its association with GC development as wells as the underlying mechanisms. GC cell lines with PDIA3 knockdown by siRNA, CRISPR-cas9 sgRNAs or a pharmacological inhibitor of LOC14 were prepared and used. PDIA3 knockout GC cells were established by CRISPR-cas9-PDIA3 system. The proliferation, migration, invasion and cell cycle of GC cells were analyzed by cell counting kit-8 assay, wound healing assay, transwell assay and flow cytometry, respectively. Immunodeficient nude mice was used to evaluate the role of PDIA3 in tumor formation. Quantitative PCR and western blot were used for examining gene and protein expressions. RNA sequencing was performed to see the altered gene expression. The expressions of PDIA3 in GC tissues and cells were increased significantly, and its expression was negatively correlated with the three-year survival rate of GC patients. Down-regulation of PDIA3 by siRNA, LOC14 or CRISPR-cas9 significantly inhibited proliferation, invasion and migration of GC cells TMK1 and AGS, with cell cycle arrested at G 2 /M phase. Meanwhile, decreased PDIA3 significantly inhibited growth of tumor xenograft in vivo. It was found that cyclin G1 (encoded by CCNG1 gene) expression was decreased by downregulation of PDIA3 in GC cells both in vitro and in vivo. In addition, protein levels of other cell cycle related factors including cyclin D1, CDK2, and CDK6 were also significantly decreased. Further study showed that STAT3 was associated with PDIA3-mediated cyclin G1 regulation. PDIA3 plays an oncogenic role in GC. Our findings unfolded the functional role of PDIA3 in GC development and highlighted a novel target for cancer therapeutic strategy. [Display omitted] • Higher PDIA3 is associated with lower survival rates in gastric cancer (GC). • PDIA3 downregulation inhibits GC cell proliferation, invasion and migration. • PDIA3 mediates G2/M cell cycle regulation though the STAT3-cyclin G1 axis. [ABSTRACT FROM AUTHOR]

Gastric Cancer (GC) is one of the most prevalent cancers worldwide. As the currently available therapeutic options are invasive, new and more benign options are being explored. One of which is Apigenin (Api), a natural flavonoid found in fruits and vegetables, such as celery, parsley, garlic, bell pepper and chamomile tea. Api has known anti-inflammatory, -oxidant, and -proliferative proprieties in several diseases and its potential as an anticancer compound has been explored. Here we systematize the available data regarding the effects of Api on GC cells, in terms of cell proliferation, apoptosis, Helicobacter pylori (H. pylori) infection, and molecular targets. From the literature it is possible to conclude that Api inhibits cell growth in a dose- and time-dependent manner, which is accompanied by the reduction of clone formation and induction of apoptosis. This occurs through the Akt/Bad/Bcl2/Bax axis that activates the mitochondrial pathway of apoptosis, resulting in restriction of cell proliferation. Additionally, it seems that the anti-proliferative potential of Api on GC cells is particularly relevant in a more aggressive GC phenotype but can also affect normal gastric cells. This indicate that this flavonoid must be used in low-to-moderate doses to avoid side-effects induced by disturbance of the normal epithelium. In H. Pylori-infected cells, the literature demonstrates that Api reduces inflammation by diminishing the levels of H. pylori colonization, by preventing NF-kB activation and by diminishing the production of reactive oxygen specimens (ROS). Accordingly, in GC Api seems to regulate different hallmarks of cancer, such as cell proliferation, apoptosis, cell migration, inflammation and oxidative stress, demonstrating its potential has an anti-GC compound. [Display omitted] • Apigenin has anti-proliferative ability towards gastric cancer cells through induction of apoptosis. • Apigenin decreases the inflammatory response to Helicobacter pylori and the production of reactive oxygen specimens. • Apigenin might be a therapeutic option to counteract progression of HP-induced inflammation into gastric cancer. • Apigenin has the potential to be used has a therapeutic option to restrain gastric cancer cell growth. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the most common and deadly cancers in women worldwide. Current treatments for breast cancer have limitations, such as toxicity, resistance, and side effects. Therefore, there is a need to develop new and effective anti-cancer agents from natural sources. Spinosyn A (SPA) is a natural product derived from soil bacteria. SPA has been reported to have anti-parasitic, insecticidal, and anti-bacterial activities. However, its anti-cancer effects and mechanisms are not well understood. In this study, we investigated the effects of SPA on T47-D, estrogen receptor-positive breast cancer cells. We found that SPA inhibited cell proliferation and migration and induced apoptosis and cell cycle arrest. Flow cytometry and holographic imaging microscopy revealed that SPA activated MAPK and PI3K signaling pathways and altered cellular morphology. Finally, RNA-Seq analysis revealed that SPA treatment altered the expression of 1380 genes in T47-D cells, which were enriched in various biological processes and signaling pathways related to cell proliferation, cholesterol metabolism, growth factor activity, amino acid transport activity, extracellular matrix, PI3K-Akt signaling pathway, neuroactive ligand-receptor interaction, and PPAR signaling pathway. Our results suggest that SPA exerts multiple anti-cancer effects on T47-D cells by modulating multiple pathways and cellular processes involved in cell growth, survival, and motility. Our findings provide new insights into the molecular mechanisms of SPA action on breast cancer cells and its potential applications as a novel anti-cancer agent. [Display omitted] • Spinosyn-A inhibits T47-D breast cancer cell proliferation and migration, promising as an anti-cancer agent. • Study shows Spinosyn-A induces apoptosis and cell cycle arrest, affecting cancer cell growth. • Spinosyn-A treatment changes T47-D cell morphology and gene expression, influencing key processes. • Transcriptomic analysis reveals over 1300 differentially expressed genes, affecting biological processes. • Spinosyn-A uniquely modulates MAPK, PI3K pathways, and oxidative stress, suggesting novel therapy. [ABSTRACT FROM AUTHOR]

Lipocalin 2 (LCN2) is a secreted glycoprotein that is produced by immune cells, including neutrophils and macrophages. It serves various functions such as transporting hydrophobic ligands across the cellular membrane, regulating immune responses, keeping iron balance, and fostering epithelial cell differentiation. LCN2 plays a crucial role in several physiological processes. LCN2 expression is upregulated in a variety of human diseases and cancers. High levels of LCN2 are specifically linked to breast cancer (BC) cell proliferation, apoptosis, invasion, migration, angiogenesis, immune regulation, chemotherapy resistance, and prognosis. As a result, LCN2 has gained attention as a potential therapeutic target for BC. This article offered an in-depth review of the advancement of LCN2 in the context of BC occurrence and development. [Display omitted] • LCN2 plays an important role in breast cancer progression. • LCN2 is involved in multiple biological processes in breast cancer. • LCN2 can be applied as a biomarker and potential target for breast cancer. [ABSTRACT FROM AUTHOR]

Ovarian cancer is one of the most lethal cancers in female reproductive system due to heterogeneity and lack of effective treatment. Targeting aerobic glycolysis, a predominant energy metabolism of cancer cells has been recognized a novel strategy to overcome cancer cell growth. However, the capability of cancer cells to undergo metabolic reprogramming guarantees their survival even when glycolysis is inhibited. Here in this study, we have shown that Cryptotanshinone (CT), a lipid-soluble bioactive anticancer molecule of Salvia miltiorrhiza, inhibits both glycolysis and oxidative phosphorylation (OXPHOS) in ovarian cancer cells leading to growth suppression and apoptosis induction. Our mechanistic study revealed that CT decreased glucose uptake and lactate production, and inhibited the kinase activity of LDHA and HK2. The molecular docking study showed that CT could directly bind with GLUT1, LDHA, HK2, PKM2 and complex-1. The immunoblotting data showed that CT decreased the expression of aberrantly activated glycolytic proteins includingGLUT1, LDHA, HK2, and PKM2. Besides, we found that CT inhibited mitochondrial ComplexⅠ activity, decreased the ratio of NAD+/NADH, and suppressed the generation of ATP and induced activation of AMPK, which controls energy-reducing processes. These in vitro findings were further validated using xenograft model. The findings of in vivo studies were in line with in vitro studies. Taken together, CT effectively suppressed glycolysis and OXPHOS, inhibited growth and induced apoptosis in ovarian cancer cells both in vitro and in vivo study models. [Display omitted] [ABSTRACT FROM AUTHOR]

Triple negative breast cancer (TNBC) poses a significant clinical challenge due to its lack of targeted therapy options and the frequent development of chemotherapy resistance. Metastasis remains a primary cause of mortality in late-stage TNBC patients, underscoring the urgent need for alternative treatments. Repurposing existing drugs offers a promising strategy for the discovery of novel therapies. In this study, we investigated the potential of pimavanserin tartrate (PVT) as a treatment for TNBC. While previous studies have highlighted PVT's anticancer effects in various cancer types, its activity in TNBC remains unclear. Our investigation aimed to elucidate the anticancer effects and underlying mechanisms of PVT in TNBC. We evaluated the impact of PVT and combination treatments involving PVT on TNBC cell viability, apoptosis, autophagy, and associated signaling pathways. Our findings revealed that PVT may induce mitochondria-dependent intrinsic apoptosis and caused cytoprotective autophagy via the PI3K/Akt/mTOR pathway in TNBC cells in vitro. Notably, our study demonstrated strong synergistic anti-TNBC effects when combining PVT with doxorubicin. We also found PVT showed some efficacies to inhibit TNBC tumor growth in vivo. These results provided valuable insights into the potential of PVT as an anti-TNBC therapeutic and a possible option for enhancing the sensitivity of TNBC cells to conventional chemotherapy drugs. Further studies are needed to determine the activity and mechanism of PVT in inhibiting TNBC. [Display omitted] • Pimavanserin triggered intrinsic apoptosis in triple negative breast cancer (TNBC) cells in vitro. • It also promoted cytoprotective autophagy of TNBC cells. • It might activate autophagy through the PI3K/Akt/mTOR pathway. • It demonstrated strong synergistic anti-TNBC properties with doxorubicin. • Pimavanserin moderately inhibited the growth of subcutaneous tumors in vivo. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • β-blockers in clinical settings can reduce the rates of progression for some tumors. • The use of integrated bioinformatical analysis combined with experimental verification is an understudied area. • Propranolol can inhibits cervical cancer cell growth by suppressing the cGMP/PKG pathway. Abstract Aim To observe the effect of propranolol in cervical cancer and investigate the mechanism of the effect． Methods and Results We found 5 direct protein targets (DPTs) of propranolol (PRO) by DrugBank5.0 firstly. Next, we analyzed protein-protein interaction (PPI) network and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of PRO DPTs and the result showed that PRO was linked with cGMP/PKG pathway. Then, we recognized the top 38 upexpressed genes of cervical cancer (CC) based original microarray datasets (GSE7803, GSE9750, GSE39001 and GSE63514). Further, we analyzed the biological process with the 38 overexpressed genes by STRING. We found some of overexpressed genes of CC participated in GMP biosynthetic process. Lastly, the function of PRO in CC was validated by MTT assay, Western blotting, flow cytometry and colony formation assay methods. We verified PRO can suppress cGMP/PKG pathway then inhibits CC cell growth. Conclusion The bioinformatical analysis combine with traditional experiment can help us understanding potential molecular mechanism about how PRO acting in CC. This method is a new paradigm which can guide future researches about mechanism in existing diseases and drugs. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Erianin cause apoptosis and cell cycle arrest in NPC cell lines. • Erianin-induced apoptosis by mitochondrial pathway and Fas-mediated pathway. • Erianin increased activation of caspase-3, -8, -9 and altered the expression of Bcl-2 family proteins in human NPC cell • Erianin induced apoptosis mediated by ERK1/2 pathway. Abstract Background Nasopharyngeal carcinoma (NPC) is one of the most common cancers in areas of Southeast Asia, such as Taiwan, and North Africa. The treatments of NPC, including radiotherapy and chemotherapy, were effective, but they also caused some severe side effects. Erianin, a natural product derived from Dendrobium, was proved to have anti-cancer effect in hepatoma, melanoma, non-small-cell lung carcinoma, myelogenous leukemia, breast cancer, and osteosarcoma. Hypothesis/Purpose According to previous research, we hypothesized that erianin inhibits cancer cell growth through apoptotic mechanisms. This study aimed to determine whether Erianin has an anti-NPC effect and what mechanisms were involved. Methods and Results The result showed that erianin significantly increased activation of apoptosis in NPC cell lines (NPC-039 and NPC-BM) and arrest the cell cycle obviously through mitochondrial membrane alternation, death receptors activation, and caspase-3, -8, -9 activation. Phosphorylated ERK1/2 was also decreased in erianin-treated NPC cell with dose-dependent manner, and the result was thought to promote apoptosis. Furthermore, the increased rate of apoptotic cells with erianin plus it's inhibitors (U) was also revealed in this study. Conclusion In conclusion, this is the first research to identify the anti-NPC effect of erianin via the apoptosis mechanism. Erianin was a promising natural agent against nasopharyngeal carcinoma. [ABSTRACT FROM AUTHOR]

Abstract Colon cancer is one of the leading causes of cancer death worldwide. Long non-coding RNA highly up-regulated in liver cancer (HULC) is an essential cancer-associated long non-coding RNA (lncRNA), contributing to the development and progression of several cancers. However, the exact effects of HULC in colon cancer progression and the underlying molecular mechanism are still unknown. In the study, we explored the detailed role of HULC in human clinical tumor tissue samples and colon cancer cell lines. The results indicated that lncRNA-HULC was markedly increased in colon cancer cell lines and accelerated colon cancer cell growth by targeting miR-613. HULC knockdown suppressed the proliferation, DNA synthesis and metastasis of human colon cancer cells in vitro. Additionally, the modulation of rhotekin (RTKN) by miR-613 was necessary in HULC-induced colon cancer cell proliferation and metastasis. The findings in the study suggested that HULC might inhibit the tumor growth through miR-613 dependent RTKN modulation. Together, our data suggested that HULC might be an oncogenic lncRNA, promoting the progression of colon cancer and could be considered as an effective therapeutic target in human colon cancer. [ABSTRACT FROM AUTHOR]

Abstract Accumulating evidences have emphasized the essential roles of differentially expressed miRNAs in papillary thyroid cancer (PTC) and follicular thyroid carcinoma (FTC) progression. MiR-128 has been reported to be down-regulated in multiple cancers to restrain tumor growth. However, the role of miR-128 in the development of PTC and FTC and the underlying mechanism remain to be unclear. In this present study, the results indicated that miR-128 expression was markedly down-regulated in PTC and FTC tissues and various thyroid carcinoma cell lines. Functional analysis indicated that over-expression of miR-128 suppressed PTC and FTC cancer cell growth, induced apoptosis and cell cycle arrest in G0/G1 phase. In addition, miR-128 over-expression markedly inhibited cancer cell migration and invasion. However, the processes above were reversed by silencing miR-128 expressions in thyroid tumor cells. Following, we characterized sphingosine kinase-1 (SPHK1) as a direct target of miR-128 that interacted with the 3′-untranslated region (UTR) of SPHK1, and the results were confirmed by using luciferase-reporter assay. We also observed that SPHK1 expression was decreased and negatively correlated with miR-128 expression in PTC and FTC tissues clinically. Importantly, ectopic expression of SPHK1 significantly abrogated the tumor-suppressive effect induced by miR-128, as supported by the reduced apoptosis, while the enhanced proliferation and metastasis. Finally, over-expressing miR-128 apparently reduced the tumor growth rate and tumor weight in vivo using xenograft tumor model, accompanied with a remarkable decrease of SPHK1. Thus, our study illustrated that miR-128 might be a tumor suppressor microRNA that played an essential role in thyroid carcinoma progression. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Colorectal cancer (CRC) is the most common carcinoma of the digestive tract. The slow growing nature of CRC offers a great opportunity for prevention strategies. The concept of chemoprevention of colorectal cancer using plant derived natural products is gaining substantial attention because it is an inherently safe and cost-effective alternative to conventional cancer therapies. Piperlongumine (PL), a natural alkaloid present in Piper longum Linn has been reported to exhibit notable anticancer effects in various in vitro studies. Nonetheless, the chemopreventive potential of PL has not been studied in experimentally induced colon cancer yet. Ras/PI3K/Akt/mTOR signaling axis plays a central role in promoting tumor cell growth, proliferation and survival by inhibiting apoptosis. In the present study, we demonstrated, for the first time, the chemopreventive effects of PL in DMH + DSS induced colon carcinogenesis animal model. We showed that PL displayed potent antineoplastic activity against colon cancer cell growth by targeting Ras proteins and PI3K/Akt signaling cascade. PL mediated inhibition of tumor cell growth was associated with inhibition of Ras protein levels and its preferred companion protein PI3K levels that led to suppressed activity of Akt/NF-κB, c-Myc and cyclin D1. It was also found that PL arrested the cell cycle progression at G2/M phase and induced mitochondrial apoptotic pathway by downregulating Bcl-2 levels. Furthermore, the results of liver and kidney toxicity suggested that PL exhibit no toxicity in animals. Our results suggest that PL may be an effective chemopreventive agent for colon cancer. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • We reported circular RNA, has_circ_0025039 in malignant melanoma. • We reported miR-198/CDK4 axis in malignant melanoma. • Has_circ_0025039 sponges miR-198 in malignant melanoma. • MiR-198 directly targets CDK4 in malignant melanoma. • Has_circ_0025039/miR-198/CDK4 axis plays critical role in malignant melanoma. Abstract Malignant melanoma, a tumor derived from melanocytes, shows severe drug resistance and prompt metastasis, causing a serious threat to human health. Circular RNAs (circRNAs) are widely expressed in mammals and have been indicated to play important roles in tumorigenesis. In the present study, we analyzed the variability of circRNAs in malignant melanoma by microarray and identified six differentially expressed circRNAs. In particular, we found that hsa_circ_0025039, which is formed by FOXM1 exons, is significantly upregulated in melanoma. In vitro, the knockdown of circ_0025039 inhibited cell proliferation, colony formation ability, invasion and glucose metabolism in melanoma cells. Additionally, we identified miR-198 as a direct target of hsa_circ_0025039. Furthermore, we demonstrated that hsa_circ_0025039 regulates CDK4 expression by sponging miR-198. In vivo study indicated that the silencing of hsa_circ_0025039 inhibits melanoma tumor formation and downregulates miR-198 and CDK4 expression. Taken together, our data showed that circ_0025039 promotes cell growth, invasion and glucose metabolism in malignant melanoma by sponging miR-198 and regulating CDK4. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • A multi-component bioactivity and structure-guided method was used to screen drugs. • SSD was identified as the most effective anti-TNBC compound from Radix Bupleuri. • SSD induced TNBC cell apoptosis via inhibiting Wnt/β-catenin signaling. • SSD did not act on EGFR and NTSR1targets. Abstract Background Triple-negative breast cancer (TNBC) is one of the most aggressive and poor prognosis breast cancers. Currently, chemotherapy with conventional cytotoxic agents is the only available option to treat TNBC. Hence, we identified new therapeutic agents against TNBC from traditional Chinese medicine Radix Bupleuri and unveiled the molecule mechanism of anti-TNBC effects. Methods Multi-component bioactivity and structure-guided methods were used to identify the most effective anti-TNBC compound Saikosaponin D (SSD) from Radix Bupleuri. Cell viability and apoptosis assays were employed to demonstrate the effect of SSD on the proliferation and apoptosis of TNBC cells. Dynamic mass redistribution assay, TopFlash assay, western blotting, and special agonist were applied to dissect the potential molecular mechanisms of SSD. Results We screened twenty fractions in Radix Bupleuri and identified SSD as the most effective component to inhibit the proliferation of TNBC cells. Investigating the interaction of SSD with the frequently overexpressed targets in TNBC led to the identification that it markedly suppressed Wnt/β-catenin signaling, but did not act on epidermal growth factor receptor and neurotensin receptor-1. Moreover, we demonstrated that SSD significantly repressed β-catenin and its downstream target genes, resulting in TNBC cell apoptosis. Specifically, docking of SSD to the crystal structure of β-catenin suggested that SSD interacted with β-catenin via hydrogen bonds and hydrophobic interaction. Conclusion We identified the most effective component SSD from Radix Bupleuri in inhibiting the proliferation of TNBC cells by targeting β-catenin signaling. Given the important role of Wnt/β-catenin signaling in breast cancer, SSD may present an opportunity to discover new therapeutics for the treatment of TNBC. [ABSTRACT FROM AUTHOR]

Highlights • RIPK4 promoted the growth and anchorage-independent growth of NPC cells. • RIPK4 promoted the expression of VEGF by activating NF-kB signaling. • Axitinib showed therapeutic effects for NPC. Abstract RIPK4 (receptor interacting serine/threonine kinase 4) has been reported to be aberrantly expressed in several cancer types. However, its expression pattern and functions in nasopharyngeal carcinoma (NPC) have never been reported. In this study, we have shown that the expression of RIPK4 was up-regulated in NPC tissues. RIPK4 promoted the growth and anchorage-independent growth of NPC cells, and down-regulation of RIPK4 inhibited the growth of NPC cells both in the plate-based culture and on the soft agar. Moreover, RIPK4 promoted the expression of VEGF in the NPC cells and induced the tube formation of HUVEC, and Axitinib (the inhibitor for VEGF receptor) inhibited the tumorigenesis driven by RIPK4. In the molecular mechanism study, RIPK4 was found to enhance the interaction between IKKα and IKKβ, and activated NF-kB signaling. Taken together, our study demonstrated the oncogenic roles of RIPK4 in NPC and suggested that RIPK4 might be a therapeutic target. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • DGD-induced apoptosis was mediated by oxidative stress. • The generation of nitrosative stress contributes to DGD-induced apoptosis. • DGD triggered an oxidative/nitrosative stress-p38 positive feedback loop. Abstract Daphnegiravone D (DGD), a prenylated flavonoid from Daphne giraldii Nitsche, significantly inhibited cell growth of several cancer cell lines without cytotoxicity on human normal cells. Our previous study showed that DGD could induce apoptosis in hepatocellular carcinoma Hep3B and HepG2 cells, but the detailed mechanism was still unclear. The present study provides that DGD-induced oxidative and nitrosative stress contribute to apoptotic cell death in Hep3B and HepG2 cells. Furthermore, there is a positive loop between oxidative stress and p38 activation, similar result is observed between nitrosative stress and p38. N-Acetylcysteine (NAC), a reactive oxygen species scavenger, could relieve DGD-induced oxidative stress, but exerts little effect on nitrosative stress. In addition, carboxy-PTIO (PTIO, a well-known scavenger of reactive nitrogen species) down-regulates the induction of nitrosative stress without obvious effect on oxidative stress in DGD-treated cells. In conclusion, the induction of oxidative and nitrosative stress could enhance p38-mediated apoptosis in DGD-treated Hep3B and HepG2 cells. Moreover, we speculated that OS and NS could not ultimately affect each other in DGD-treated HCC cells. This study gives a new insight on the mechanism of DGD-induced apoptotic cell death via oxidative and nitrosative stress in HCC cells. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) play important roles in tumor progression. Recently, increasing evidence showed that lncRNA NORAD could be used as an important regulator in tumor progression. However, the roles and underlying mechanism of NORAD in cervical cancer (CC) remain unclear. In the present study, we found that NORAD expression was significantly up-regulated in CC tissues and cell lines. High NORAD expression was correlated with advanced FIGO stage, lymph nodes metastasis, vascular invasion, and poor overall survival of CC patients. In vitro function assays, we showed that NORAD suppression reduced CC cells proliferation, invasion, and epithelial-mesenchymal transition (EMT) processes. Furthermore, the underlying mechanism studies showed that lncRNA NORAD could sponge miR-590-3p to promote the proliferation and invasion of CC cells via upregulating SIP1 expression. In addition, we showed that NORAD inhibition could reduce CC cells growth in vivo. Taken together, these results suggested that NORAD could serve as a ceRNA in CC progression by modulating miR-590-3p/SIP1 axis and act as a therapeutic target for the treatment of CC. [ABSTRACT FROM AUTHOR]

Disparate roles exist for tumor-associated macrophages in breast cancer growth and progression. The aim of this study was to explore the influence of induced macrophages on the growth of breast cancer cells. THP-1 monocytes were differentiated to macrophages using phorbol 12-myristate 13-acetate. The effect of the medium from THP-1 monocytes or macrophage-conditioned medium (MφCM) on MCF-7 (estrogen receptor and progesterone-positive positive) and MDA-MB-231 (MB; triple-negative) breast cancer cells was determined at 24 h, 48 h and 72 h. Assays were conducted for cell viability, apoptosis, proliferation and cell phenotype, and quantitative real-time polymerase chain reaction (qRT-PCR) for expression of associated genes. MφCM inhibited proliferation of MCF-7 and MB cells in a time-dependent manner and, in particular, decreased viability of MCF-7 cells. MφCM induced a markedly vacuolated phenotype in MCF-7 increased apoptosis in MCF-7 cells, but correlative changes in Bcl-2 or Bax were absent. A multifold and significant reduction in anti-apoptotic Bcl-2 in MB cells was not matched by increased apoptosis. The cell cycle inhibitor CDKN1A was increased in both cell lines, but PCNA decreased only in MB cells. Senescence-associated galactosidase beta-1 (GLB1) mRNA was decreased in MCF-7 cells (48 and 72 h) but increased in MB cells (72 h). Increased expression of interleukin-6 (IL-6) and IL-8 was seen in both cell lines, and increased tumor necrosis factor- α was seen at 24 h for MB and 72 h for MCF-7 indicating increased inflammatory responses of the cancer cells. The two breast cancer celllines had different responses to MφCM, mainly involving inhibition rather than stimulation of growth of the cells, stimulation of senescence (MB cells) and increased inflammatory cytokine expression. The estrogen and progesterone receptor status of the cell lines may determine their response to MφCM. The function of the inflammatory cytokines in breast cancer growth remains to be identified. [ABSTRACT FROM AUTHOR]

Dendrobium, which belongs to the family of Orchidaceae, is a highly valuable traditional Chinese medicine commonly used in China. It exerts pharmacological activities such as antitumor and hypoglycemia effects, and its main components are alkaloids, polysaccharides, and terpenoids, among others. In recent years, research on the clinical application of Dendrobium in antitumor therapy has gained increasing attention. Accumulating evidence suggests that the active components of Dendrobium possess significant inhibitory effects on the viability of cancer cells as evident from in vivo and in vitro experiments, which indicates that Dendrobium exerts significant anticancer effect in treating and preventing cancer development, inhibiting the underlying potential molecular mechanisms, including suppression of cancer cell growth and proliferation, epithelial-mesenchymal transition (EMT), apoptosis induction, tumor angiogenesis, and reinforcement of cisplatin (DDP) -induced apoptosis. We herein present a review that summarizes the research progress of the application of Dendrobium in cancer therapy and its molecular mechanisms. This review describes the positive aspects of the active ingredients of Dendrobium in the treatment of cancers in various systems of the human body, their inhibitory effects on tumor survival and tumor microenvironment, and their potential mechanisms. Additionally, this review proposes future application prospects of Dendrobium in cancer therapy to promote further research and future extensive clinical applications of Dendrobium in cancer therapy. [ABSTRACT FROM AUTHOR]

Plant bioactive molecules could play key preventive and therapeutic roles in chronological aging and the pathogenesis of many chronic diseases, often accompanied by increased oxidative stress and low-grade inflammation. Dietary antioxidants, including genkwanin, could decrease oxidative stress and the expression of pro-inflammatory cytokines or pathways. The present study is the first comprehensive review of genkwanin, a methoxyflavone found in several plant species. Indeed, natural sources, and pharmacokinetics of genkwanin, the biological properties were discussed and highlighted in detail. This review analyzed and considered all original studies related to identification, isolation, quantification, investigation of the biological and pharmacological properties of genkwanin. We consulted all published papers in peer‐reviewed journals in the English language from the inception of each database to 12 May 2023. Different phytochemical demonstrated that genkwanin is a non-glycosylated flavone found and isolated from several medicinal plants such as Genkwa Flos , Rosmarinus officinalis, Salvia officinalis , and Leonurus sibiricus. In vitro and in vivo biological and pharmacological investigations showed that Genkwanin exhibits remarkable antioxidant and anti-inflammatory activities, genkwanin, via activation of glucokinase, has shown antihyperglycemic activity with a potential role against metabolic syndrome and diabetes. Additionally, it revealed cardioprotective and neuroprotective properties, thus reducing the risk of cardiovascular diseases and assisting against neurodegenerative diseases. Furthermore, genkwanin showed other biological properties like antitumor capability, antibacterial, antiviral, and dermato-protective effects. The involved mechanisms include sub-cellular, cellular and molecular actions at different levels such as inducing apoptosis and inhibiting the growth and proliferation of cancer cells. Despite the findings from preclinical studies that have demonstrated the effects of genkwanin and its diverse mechanisms of action, additional research is required to comprehensively explore its therapeutic potential. Primarily, extensive studies should be carried out to enhance our understanding of the molecule's pharmacodynamic actions and pharmacokinetic pathways. Moreover, toxicological and clinical investigations should be undertaken to assess the safety and clinical efficacy of genkwanin. These forthcoming studies are of utmost importance in fully unlocking the potential of this molecule in the realm of therapeutic applications. [Display omitted] • Genkwanin possesses a potent anti-inflammatory effect by inhibiting inflammatory mediators and pathways. • Genkwanin acts as an antioxidant, protecting cells from oxidative stress and scavenging free radicals. • Genkwanin exhibits anticancer properties by inhibiting tumor cell proliferation, inducing apoptosis, and suppressing angiogenesis. • Genkwanin exerts neuroprotective effects by reducing oxidative stress, inhibiting neuroinflammation, and modulating neuronal signaling pathways. • Genkwanin shows promising anti-diabetic effects by enhancing insulin sensitivity, regulating glucose metabolism, and reducing oxidative stress associated with diabetes. [ABSTRACT FROM AUTHOR]

Ellagic acid (EA) is a kind of polyphenol compound extracted from a variety of herbs, such as paeoniae paeoniae, raspberry, Chebule, walnut kernel, myrrh, loquat leaf, pomegranate bark, quisquite, and fairy herb. It has anti-tumor, anti-oxidation, anti-inflammatory, anti-mutation, anti-bacterial, anti-allergic and multiple pharmacological properties. Studies have shown its anti-tumor effect in gastric cancer, liver cancer, pancreatic cancer, breast cancer, colorectal cancer, lung cancer and other malignant tumors, mainly through inducing tumor cell apoptosis, inhibiting tumor cell proliferation, inhibiting tumor cell metastasis and invasion, inducing autophagy, affecting tumor metabolic reprogramming and other forms of anti-tumor efficacy. Its molecular mechanism is mainly reflected in inhibiting the proliferation of tumor cells through VEGFR-2 signaling pathway, Notch signaling pathway, PKC signaling pathway and COX-2 signaling pathway. PI3K/Akt signaling pathway, JNK (cJun) signaling pathway, mitochondrial pathway, Bcl-2 / Bax signaling pathway, TGF-β/Smad3 signaling pathway induced apoptosis of tumor cells and blocked EMT process and MMP SDF1α/CXCR4 signaling pathway inhibits the metastasis and invasion of tumor cells, induces autophagy and affects tumor metabolic reprogramming to produce anti-tumor effects. At present, the analysis of the anti-tumor mechanism of ellagic acid is slightly lacking, so this study comprehensively searched the literature on the anti-tumor mechanism of ellagic acid in various databases, reviewed the research progress of the anti-tumor effect and mechanism of ellagic acid, in order to provide reference and theoretical basis for the further development and application of ellagic acid. [ABSTRACT FROM AUTHOR]

Gastric cancer is a common gastrointestinal malignancy worldwide, with a high mortality rate and poor prognosis. Multidrug resistance remains a major obstacle to successful treatment for patients. Hence, it is of great significance to develop novel therapies to potentiate the anti-tumor effect. In this study, we have investigated the effect of estradiol cypionate (ECP) on gastric cancer in vitro and vivo. Our data show that ECP inhibited the proliferation, promoted apoptosis, and caused G1/S phase arrest of gastric cancer cells. The mechanism by which ECP promoted apoptosis of gastric cancer cells was related to the downregulation of AKT protein expression caused by the increased ubiquitination modification levels of AKT, which finally inhibited the over-activation of the PI3K-AKT-mTOR signaling pathway. In vivo tumorigenesis experiments showed that ECP significantly inhibited the growth of gastric cancer cells, showing promise for clinical application. The above findings indicate that ECP inhibited the growth of gastric cancer and induced apoptosis through the PI3K /Akt/mTOR pathway. In summary, the efficacy showed in our data suggests that ECP is a promising anti-tumor compound for gastric cancer. • Estradiol cypionate（ECP）suppresses proliferation of gastric cancer cells. • ECP induces cell cycle arrest and apoptosis in gastric cancer cells. • The anticancer mechanism of ECP is linked to PI3K/Akt/mTOR signaling • pathway. • ECP suppressed tumor growth in the xenograft model. [ABSTRACT FROM AUTHOR]

Currently, there are several treatments approaches available for lung cancer; however, patients who develop drug resistance or have poor survival rates urgently require new therapeutic strategies for lung cancer. In autophagy, damaged proteins or organelles are enclosed within autophagic vesicles with a bilayer membrane structure and transported to the lysosomes for degradation and recirculation. Autophagy is a crucial pathway involved in the clearance of reactive oxygen species (ROS) and damaged mitochondria. Meanwhile, inhibiting autophagy is a promising strategy for cancer treatment. In this study, we found for the first time that Cinchonine (Cin) can act as an autophagy suppressor and exert anti-tumor effects. Cin significantly inhibited the proliferation, migration, and invasion of cancer cells in vitro and the tumor growth and metastasis in vivo , without obvious toxic effects. We found that Cin suppressed the autophagic process by blocking autophagosome degradation through the inhibition of the maturation of lysosomal hydrolases. Cin-mediated autophagy inhibition resulted in the elevated ROS level and the accumulation of damaged mitochondria, which in turn promoted apoptosis. N-acetylcysteine, a potential ROS scavenger, significantly suppressed Cin-induced apoptosis. Additionally, Cin upregulated programmed death-ligand 1 (PD-L1) expression in lung cancer cells by inhibiting autophagy. Compared with monotherapy and control group, the combined administration of anti-PD-L1 antibody and Cin significantly reduced tumor growth. These results suggest that Cin exerts anti-tumor effects by inhibiting autophagy, and that the combination of Cin and PD-L1 blockade has synergistic anti-tumor effects. The data demonstrates the significant clinical potential of Cin in lung cancer treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the second most fatal disease and is the prime cause of cancer allied female deaths. BC is caused by aberrant tumor suppressor genes and oncogenes regulated by transcription factors (TFs) like NF-κB. NF-κB is a pro-inflammatory TF that crucially alters the expressions of various genes associated with inflammation, cell progression, metastasis, and apoptosis and modulates a network of genes that underlie tumorigenesis. Herein, we focus on NF-κB signaling pathways, its regulators, and the rationale for targeting NF-κB. This review also includes TFs that maintain NF-κB crosstalk and their roles in promoting angiogenesis and metastasis. In addition, we discuss the importance of combination therapies, resistance to treatment, and potential novel therapeutic strategies including nanomedicine that targets NF-κB. [Display omitted] • Current insight and updates on the mechanism of NF-κB signaling pathways regulation. • Mechanism of crosstalk between NF-κB and various TFs and their role in promoting metastasis. • Detailed analysis on NF-κB targeted strategies to overcome chemoresistance in BC. • We discuss various combinational therapies and latest clinical trials conducted in BC. [ABSTRACT FROM AUTHOR]

There is growing evidence showing that single administration of immunotherapeutic agents has limited efficacy in a number of cancer patients mainly due to tumor heterogeneity and immunosuppressive tumor microenvironment. In this study, a novel nanoparticle-based strategy was applied to achieve efficient tumor-targeted therapy by combining chemotherapeutic agents, i.e., doxorubicin (Dox) and melittin (Mel), with an immune checkpoint inhibitor (PD-L1 DsiRNA). The proposed nanoparticle was prepared by the formation of a complex between Mel and PD-L1 DsiRNA (Dicer-substrate short-interfering RNA), followed by the loading of Dox. The surface of the resultant particles (DoxMel/PD-L1 DsiRNA) was then modified with hyaluronic acid (HA) to increase their stability and distribution. In addition, HA can also act as a tumor-targeting agent through binding to its receptor CD44 on the surface of cancer cells. We demonstrated that the surface engineering of DoxMel/PD-L1 DsiRNA with HA significantly enhances its specificity towards breast cancer cells. Moreover, we observed a noticeable reduction in PD-L1 expression together with a synergistic effect of Dox and Mel on killing cancer cells and inducing immunogenic cell death, leading to significantly diminished tumor growth in 4T1-breast tumor bearing Balb/c mice, improved survival rate and extensive infiltration of immune cells including cytotoxic T cells into the tumor microenvironment. Safety analysis revealed that there is no significant toxicity associated with the developed nanoparticle. All in all, the proposed targeted combination treatment strategy can be considered as a useful method to reduce cancer-associated mortality. • A novel nanoparticle-based chemo-immunotherapy (DoxMel/PD-L1 DsiRNA@HA) for breast cancer was developed. • DoxMel/PD-L1 DsiRNA@HA significantly suppressed both primary and distant breast tumors in tumor-bearing Balb/c mice. • Induction of ICD along with suppression of PD-L1 expression by DoxMel/PD-L1 DsiRNA@HA led to a robust systemic immunity against cancer cells. • DoxMel/PD-L1 DsiRNA@HA has high potential for future clinical translation due to its high safety profile and strong anti-tumor efficacy. [ABSTRACT FROM AUTHOR]

PF-543 is a sphingosine kinase 1（SPHK1）inhibitor developed by Pfizer and is currently considered the most potent selective SPHK1 inhibitor. SPHK1 catalyses the production of sphingosine 1-phosphate (S1P) from sphingosine. It is the rate-limiting enzyme of S1P production, and there is substantial evidence to support a very important role for sphingosine kinase in health and disease. This review is the first to summarize the role and mechanisms of PF-543 as an SPHK1 inhibitor in anticancer, antifibrotic, and anti-inflammatory processes, providing new therapeutic leads and ideas for future research and clinical trials. [Display omitted] • This article is the first comprehensive review on PF-543. • PF-543 is a drug with therapeutic potential. • PF-543 exerts various biological functions, such as Inhibits cancer cell growth, antifibrotic and anti-inflammatory. [ABSTRACT FROM AUTHOR]

Dysregulation of mircoRNAs (miRs) that act as tumor suppressors or oncogenes is participated in tumorigenesis and progression. The aim of the study is to investigate the role and mechanism of miR-1297 in gastric cancer (GC). Here, we demonstrated that miR-1297 expression was significantly lower in GC tissue samples compared to adjacent normal tissue samples in 62 cases GC patients. Lower miR-1297 expression positively associated with larger tumor size, lymph node metastasis, advanced TNM stage and poor survival time of patients. Upregulation of miR-1297 significantly inhibited cell proliferation and cell colony forming abilities in vitro. However, downregulation of miR-1297 can cause the reverse biological function changes. In vivo, miR-1297 overexpression suppressed tumor growth. Luciferase reporter assay showed that CREB1 was a direct target of miR-1297 in GC. MiR-1297 inhibited the expression of CREB1 by targeting the 3’UTR of CREB1. Additionally, we demonstrated that CREB1 overexpression rescued the effects on GC cell growth induced by miR-1297. Therefore, these results indicated that miR-1297 might be a prognostic predictor for GC and potential target of GC treatment. [ABSTRACT FROM AUTHOR]

Cancer is world’s second largest alarming disease, which involves abnormal cell growth and have potential to spread to other parts of the body. Most of the available anticancer drugs are designed to act on specific targets by altering the activity of involved transporters and genes. As cancer cells exhibit complex cellular machinery, the regeneration of cancer tissues and chemo resistance towards the therapy has been the main obstacle in cancer treatment. This fact encourages the researchers to explore the multitargeted use of existing medicines to overcome the shortcomings of chemotherapy for alternative and safer treatment strategies. Recent developments in genomics-proteomics and an understanding of the molecular pharmacology of cancer have also challenged researchers to come up with target-based drugs. The literature supports the evidence of natural compounds exhibiting antioxidant, antimitotic, anti-inflammatory, antibiotic as well as anticancer activity. In this review, we have selected marine sponges as a prolific source of bioactive compounds which can be explored for their possible use in cancer and have tried to link their role in cancer pathway. To prove this, we revisited the literature for the selection of cancer genes for the multitargeted use of existing drugs and natural products. We used Cytoscape network analysis and Search tool for retrieval of interacting genes/ proteins (STRING) to study the possible interactions to show the links between the antioxidants, antibiotics, anti-inflammatory and antimitotic agents and their targets for their possible use in cancer. We included total 78 pathways, their genes and natural compounds from the above four pharmacological classes used in cancer treatment for multitargeted approach. Based on the Cytoscape network analysis results, we shortlist 22 genes based on their average shortest path length connecting one node to all other nodes in a network. These selected genes are CDKN2A, FH, VHL, STK11, SUFU, RB1, MEN1, HRPT2, EXT1, 2, CDK4, p14, p16, TSC1, 2, AXIN2, SDBH C, D, NF1, 2, BHD, PTCH, GPC3, CYLD and WT1. The selected genes were analysed using STRING for their protein-protein interactions. Based on the above findings, we propose the selected genes to be considered as major targets and are suggested to be studied for discovering marine natural products as drug lead in cancer treatment. [ABSTRACT FROM AUTHOR]

Rosmarinic acid (RA), isolated from herbal balm mint plants, has demonstrated potent anti-tumor properties against liver cancer. However, the precise underlying mechanisms remain unclear. This study aimed to investigate the molecular mechanisms of RA in HepG2 cells. RA anti-tumor activity was assessed using 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays, and Hoechst 33258 staining. Apoptosis and the cell cycle distribution were evaluated by flow cytometry. A proteomics approach was used to identify differentially expressed proteins following RA treatment in HepG2 cells, and quantitative reverse transcription–quantitative polymerase chain reaction was used to validate the results. Bioinformatics analysis was also implemented to further understand the identified proteins, and western blotting was used to analyze the associated proteins. Our results suggested that RA treatment significantly inhibits the viability of HepG2 cells. The MTT and LDH assays indicated dose-dependent decreases in cell proliferation following RA treatment. Hoechst 33258 staining and flow cytometry analysis showed that RA exhibits an apoptosis-inducing effect and induces cell cycle arrest in G1. The proteomics analysis successfully identified 16 differentially expressed proteins. Bioinformatics analysis indicated that the identified proteins participated in several biological processes and exhibited various molecular functions, mainly related to inactivation of the glycolytic pathway. Further western blotting analysis showed that RA could downregulate the expression of glucose transporter-1 and hexokinase-2, leading to the suppression of glucose consumption and generation of lactate and ATP. Taken together, our study found that RA exhibits significant cytotoxic effects by inhibiting cell proliferation and inducing apoptosis and cell cycle arrest, possibly by blocking the glycolytic pathway in human HepG2 cells. [ABSTRACT FROM AUTHOR]

Gastric cancer is a most common malignancy and the third leading cause of cancer mortality worldwide. So it is important to identify the prognostic markers and effective therapeutic targets against gastric cancer. miRNA plays an important role in tumor cell cycle, differentiation, apoptosis, invasion and metastasis. Many studies devote to the mechanism of miRNA regulates gastric cancer carcinoma and progression. In the present study, we found that the level of miR-518 in gastric cancer and cell lines were lower than the control or the adjacent tissues by qRT-PCR. Transfected with miR-518 mimic trigger apoptosis in MKN45 and HGC27 gastric cancer cell in vitro and in vivo . Moreover, we found that MDM2 was negatively regulated by miR-518 via targeting 26–32 site of 3’UTR using luciferase reporter assay. The western blot assay showed that miR-518 up-regulated the expression of p53, pro-apoptotic protein Bax and active the activity of cleaved caspase-3, down-regulated expression of anti-apoptotic protein Bcl-2 via targeting MDM2. Thus, our study suggested that miR-518 acted as a new tumor suppressor by targeting MDM2 gene and trigger apoptosis in vivo and in vit ro . The findings of the study first established the role of miR-518 in gastric cancer and may be a potential therapeutic target against gastric cancer in the further. [ABSTRACT FROM AUTHOR]

Our previous work has demonstrated that miR-323 enhances tumor angiogenesis in prostate cancer. In the present study, we sought to determine the function of miR-323 in prostate cancer cell growth and response to docetaxel. The effects of miR-323 overexpression on prostate cancer cell proliferation, colony formation, and tumorigenesis were examined. We also investigated the impact of miR-323 knockdown on cell cycle progression and apoptosis. Ectopic expression of miR-323 promoted cell proliferation and colony formation in vitro and xenograft tumor growth in vivo. Depletion of miR-323 arrested PC-3 prostate cancer cells at the G0/G1 phase and caused significant apoptosis, which was coupled with increased expression of p21 and cleavage of caspase-9 and caspase-3 and reduced expression of cyclin D1. Compared to PC-3 parental cells, docetaxel-resistant PC-3-DR cells had 5.6-fold higher levels of miR-323. Overexpression of miR-323 increased the 50% inhibitory concentration (IC 50 ) value for docetaxel in PC-3 cells, while silencing of miR-323 exerted an opposite effect on PC-3-DR cells. Mechanistically, miR-323 repressed the expression of p73 in prostate cancer cells. Knockdown of p73 augmented cell proliferation and colony formation and blunted sensitivity to docetaxel in PC-3 cells. In addition, overexpression of p73 significantly suppressed cell proliferation and induced apoptosis and docetaxel sensitivity in PC-3-DR cells. In conclusion, miR-323 contributes to the aggressive phenotype of prostate cancer cells by targeting p73 and represents a potential therapeutic target for this malignancy. [ABSTRACT FROM AUTHOR]

Background One approach to improve effect of chemotherapy is combination of classical cytostatic drugs with natural compounds, e. g. sesquiterpenes. In our previous study, sesquiterpenes β-caryophyllene oxide (CAO) and trans -nerolidol (NER) improved the anti-proliferative effect of doxorubicin (DOX) in intestinal cancer cell lines. Purpose The present study was designed to evaluate the effect of CAO and NER on DOX efficacy, focusing on cell proliferation, migration, apoptosis and DOX accumulation in breast cancer cells MDA-MB-231 and MCF7 in vitro and in mice bearing solid Ehrlich tumors (EST) in vivo . Methods The impact of cytotoxic effect was assessed by the neutral red uptake test. The ability to migrate was tested using real-time measurement in x-CELLigence system. Expressions of molecules were examined using western blot analysis. The accumulation of DOX inside the cells using time lapse microscopy was observed. The mice with inoculated EST cells were treated repeatedly with DOX and DOX + CAO or DOX + NER and the growth of tumors were monitored. DOX concentrations in plasma and tumor were assayed using HPLC. Results In MDA-MB-231, combination of DOX with CAO enhanced anti-proliferative effect and acted strongly synergistic. NER increased accumulation of DOX inside the cells; moreover combination DOX with NER suppressed migration ability in vitro . In vivo , apoptosis was activated especially in group treated with DOX and CAO. However, none of tested sesquiterpenes was able to improve DOX accumulation in tumors and DOX-mediated inhibition of tumor growth. Conclusion In conclusion, sesquiterpenes CAO and NER increased the efficacy of DOX in breast cancer cells in vitro , but did not improve its effect in vivo , in Ehrlich solid tumor bearing mice. [ABSTRACT FROM AUTHOR]

With the rapid development of next-generation sequencing technology, several studies have shown that ncRNAs can act as competitive endogenous RNAs (ceRNAs) and are involved in various biological processes, such as proliferation, differentiation, apoptosis, and migration of breast cancer (BC) cells, and plays an important role in BC progression as a molecular target for its diagnosis, treatment, prognosis, and differentiation of subtypes and age groups of BC patients. Based on the description of ceRNA-related biological functions, this study screened and sorted the sequencing analysis and experimental verification conclusions of BC-related ceRNAs and found that the ncRNAs mediated ceRNA networks can promote the development of BC by promoting the expression of genes related to BC proliferation, drug resistance, and apoptosis, inducing the production of epithelial-mesenchymal transition (EMT) to promote metastasis and activating cancer-related signaling pathways. [Display omitted] • ncRNA-mediated ceRNA networks is involved in various biological processes of breast cancer. • ncRNA-mediated ceRNA networks play a crucial role in diagnosis of breast cancer. • ncRNA-mediated ceRNA networks may facilitate the development of new anti-tumor drugs and clinical interventions of breast cancer. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the most common cancer in women worldwide. Although substantial progress has been made in the diagnosis and treatment of breast cancer, the efficacy and side effects of traditional treatment methods are still unsatisfactory. In recent years, immunotherapy including tumor vaccine has achieved great success in the treatment of BC. Dendritic cells (DCs) are multifunctional antigen-presenting cells that play an important role in the initiation and regulation of innate and adaptive immune responses. Numerous studies have shown that DC-based treatments might have a potential effect on BC. Among them, the clinical study of DC vaccine in BC has demonstrated considerable anti-tumor effect, and some DC vaccines have entered the stage of clinical trials. In this review, we summarize the immunomodulatory effects and related mechanisms of DC vaccine in breast cancer as well as the progress of clinical trials to propose possible challenges of DC vaccines and new development directions. [ABSTRACT FROM AUTHOR]

Breast cancer is the leading cancer in women. Around 20–30% breast cancer patients undergo invasion or metastasis after radical surgical resection and eventually die. Number of breast cancer patients show poor sensitivity toward treatments despite the advances in chemotherapy, endocrine therapy, and molecular targeted treatments. Therapeutic resistance and tumor recurrence or metastasis develop with the ongoing treatments. Conducive treatment strategies are thus required. Chimeric antigen receptor (CAR)-modified T-cell therapy has progressed as a part of tumor immunotherapy. However, CAR-T treatment has not been effective in solid tumors because of tumor microenvironment complexity, inhibitory effects of extracellular matrix, and lacking ideal tumor antigens. Herein, the prospects of CAR-T cell therapy for metastatic breast cancer are discussed, and the targets for CAR-T therapy in breast cancer (HER-2, C-MET, MSLN, CEA, MUC1, ROR1, EGFR) at clinical level are reviewed. Moreover, solutions are proposed for the challenges of breast cancer CAR-T therapy regarding off-target effects, heterogeneous antigen expression by tumor cells and immunosuppressive tumor microenvironment. Ideas for improving the therapeutics of CAR-T cell therapy in metastatic breast cancer are suggested. • The prospects of CAR-T for metastatic breast cancer and its use in clinical treatment of breast cancer are reviewed. • The solutions are proposed for the challenges of breast cancer CAR-T therapy. • Ideas are suggested for improving the therapeutics of CAR-T cell therapy in metastatic breast cancer. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the most frequently occurring cancer type seriously threatening the lives of women worldwide. Clinically, the high frequency of diverse resistance to current therapeutic strategies advocates a demand to develop novel and effective approaches for the efficient treatment of BC. The chimeric antigen receptor T (CAR-T) cells therapy, one of the immunotherapies, has displayed powerful capacity to specifically kill and eliminate tumors. Due to the success of CAR-T therapy achieved in treating hematological malignancy, the effect of CAR-T cells therapy has been tested in various human diseases including breast cancer. This review summarized and discussed the landscape of the CAR-T therapy for breast cancer, including the advances, challenge and countermeasure of CAR-T therapy in research and clinical application. The roles of potential antigen targets, tumor microenvironment, immune escape in regulating CAR-T therapy, the combination of CAR-T therapy with other therapeutic strategies to further enhance therapeutic efficacy of CAR-T treatment were also highlighted. Therefore, our review provided a comprehensive understanding of CAR-T cell therapy in breast cancer which will awake huge interests for future in-depth investigation of CAR-T based therapy in cancer treatment. [Display omitted] • The development of CAR-T cells therapy and its application in breast cancer were comprehensive summarized • High heterogeneity, suppressive tumor microenvironment and immune escape are critical challenges of CAR T therapy in BC. • The combination of CRISPR systems, immune checkpoint blockade and radiation improved the effect of CAR-T cell therapy. • The strategies of targets optimization, next generation CARs and clinical trials are also expounded. [ABSTRACT FROM AUTHOR]

As a devastating disease, breast cancer has been responsible for decrease in life expectancy of females and its morbidity and mortality are high. Breast cancer is the most common tumor in females and its treatment has been based on employment of surgical resection, chemotherapy and radiotherapy. The changes in biological behavior of breast tumor relies on genomic and epigenetic mutations and depletions as well as dysregulation of molecular mechanisms that autophagy is among them. Autophagy function can be oncogenic in increasing tumorigenesis, and when it has pro-death function, it causes reduction in viability of tumor cells. The carcinogenic function of autophagy in breast tumor is an impediment towards effective therapy of patients, as it can cause drug resistance and radio-resistance. The important hallmarks of breast tumor such as glucose metabolism, proliferation, apoptosis and metastasis can be regulated by autophagy. Oncogenic autophagy can inhibit apoptosis, while it promotes stemness of breast tumor. Moreover, autophagy demonstrates interaction with tumor microenvironment components such as macrophages and its level can be regulated by anti-tumor compounds in breast tumor therapy. The reasons of considering autophagy in breast cancer therapy is its pleiotropic function, dual role (pro-survival and pro-death) and crosstalk with important molecular mechanisms such as apoptosis. Moreover, current review provides a pre-clinical and clinical evaluation of autophagy in breast tumor. [Display omitted] [ABSTRACT FROM AUTHOR]

Background and amid Multidrug resistance (MDR) is the main obstacle to successful chemotherapy for patients with gastric cancer (GC). The GHET1 affects a variety of cancer development, and increased GHET1 promotes gastric carcinoma cell proliferation. This study amid to investigate the effect of GHET1 on the development of MDR in gastric cancer cells. Methods and results In this study, we observed an increased expression levels of GHET1 in drug-resistant gastric cancer patients and cisplatin-resistant gastric cancer cell lines (BGC823/DPP and SGC7901/DDP cell line). Next, the two cell lines were used to in vitro validation of the effect of GHET1 expression on the MDR development. Silence of GHET1 in the two cisplatin-resistant gastric cancer cell lines inhibited the MDR with rising inhibition rate tested by MTT (methyl thiazolyl tetrazolium) assay. The apoptotic cell rate was analyzed by staining with Annexin V/PI. The results showed that the IC50 (half maximal inhibitory concentration) of the two cisplatin-resistant gastric cancer cell lines transfected with si-GHET1 were significantly reduced. Contrary to inhibition of GHET1 in the two cisplatin-resistant gastric cancer cell lines, we found that overexpression of GHET1 reduced sensitivity of BGC823 and SGC7901 cells to cisplatin with decreased inhibition rate and apoptotic cell rate and increased IC50. Furthermore, the qRT–PCR and western blot results showed that overexpression of GHET1 downregulated Bax expression and upregulated Bcl-2, MDR1 and MRP1 expression in BGC823 and SGC7901 cells. Conclusion Highly expressing GHET1 promoted the development of MDR which was related to the Bax, Bcl-2, MDR1 and MRP1 genes expression in gastric cancer cells. [ABSTRACT FROM AUTHOR]

Progestin and AdipoQ Receptor 3 (PAQR3), a member of the PAQR family, is down-regulated in several types of cancers and has been closely associated with tumor progression and development. However, little is known about the functions of PAQR3 in the tumorigenesis of human glioma. Therefore, in this report, we investigated the role of PAQR3 in human glioma. Our results showed that the expression of PAQR3 was significantly reduced in human glioma tissues and cell lines. PAQR3 overexpression inhibited the proliferation of glioma cells in vitro and attenuated tumor xenograft growth in vivo . In addition, PAQR3 overexpression suppressed the migration and invasion of glioma cells, as well as prevented the EMT process. Mechanistic studies demonstrated that PAQR3 overexpression significantly down-regulated the levels of phosphorylated PI3K and Akt in U251 cells. In conclusion, these results demonstrated that PAQR3 inhibited the proliferation, migration and invasion in glioma cells, at least in part, through the inactivation of PI3K/Akt signaling pathway. Therefore, PAQR3 may be a therapeutic target for the treatment of glioma. [ABSTRACT FROM AUTHOR]