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Stem cell-based therapies hold significant potential for cancer treatment due to their unique properties, including migration toward tumor niche, secretion of bioactive molecules, and immunosuppression. Mesenchymal stem cells (MSCs) from adult tissues can inhibit tumor progression, angiogenesis, and apoptosis of cancer cells. We have previously reported the isolation and characterization of placenta-derived decidua basalis mesenchymal stem cells (DBMSCs), which demonstrated higher levels of pro-migratory and anti-apoptotic genes, indicating potential anti-cancer effects. In this study, we analyzed the anti-cancer effects of DBMSCs on human breast cancer cell lines MDA231 and MCF7, with MCF 10A used as control. We also investigated how these cancer cells lines affect the functional competence of DBMSCs. By co-culturing DBMSCs with cancer cells, we analyzed changes in functions of both cell types, as well as alterations in their genomic and proteomic profile. Our results showed that treatment with DBMSCs significantly reduced the functionality of MDA231 and MCF7 cells, while MCF 10A cells remained unaffected. DBMSC treatment decreased epithelial-to-mesenchymal transition (EMT)-related protein levels in MDA231 cells and modulated expression of other cancer-related genes in MDA231 and MCF7 cells. Although cancer cells reduced DBMSC proliferation, they increased their expression of anti-apoptotic genes. These findings suggest that DBMSCs can inhibit EMT-related proteins and reduce the invasive characteristics of MDA231 and MCF7 breast cancer cells, highlighting their potential as candidates for cell-based cancer therapies. [ABSTRACT FROM AUTHOR]

Despite significant efforts, cancer remains the second leading cause of mortality worldwide. The medicinal plant Nepeta nuda L. represents a valuable source of biologically active compounds with pharmacological activities including antioxidant, anti-inflammatory, antimicrobial, and antiviral. This study aimed to assess the antiproliferative potential and mechanisms of action of aqueous extract from the leaves of wild-grown N. nuda. Cancer cell lines, MDA-MB-231, MCF7 (breast), HT29, Colon 26 (colon), and HepG2 (liver cancer), and a non-cancerous skin cell line, BJ, were assessed for antiproliferative activity by MTT assay and observation of cell morphological alterations. The cancer cell line that was most sensitive to the extract was further studied for apoptotic alterations by Annexin V/propidium iodide staining, colony-forming assay, and qRT-PCR analysis. The results revealed that the plant extract inhibited the proliferation of all investigated cancer cell lines with the strongest cytostatic effect on Colon 26 cells with a half maximal inhibitory concentration (IC50) value of 380.2 μg/mL and a selectivity index (SI) of 3.5. The extract significantly inhibited the ability of cells to form colonies, exhibited considerable proapoptotic potential involving the participation of the CASP8 gene, and increased the expression levels of ATG3 and the BECN1 gene, which suggests a role of autophagic cell death in the antitumor action. [ABSTRACT FROM AUTHOR]

Breast cancer, a predominant global health issue, requires ongoing exploration of new therapeutic strategies. Palbociclib (PAL), a well-known cyclin-dependent kinase (CDK) inhibitor, plays a critical role in breast cancer treatment. While its efficacy is recognized, the interplay between PAL and cellular autophagy, particularly in the context of the RAF/MEK/ERK signaling pathway, remains insufficiently explored. This study investigates PAL's inhibitory effects on breast cancer using both in vitro (MCF7 and MDA-MB-468 cells) and in vivo (tumor-bearing nude mice) models. Aimed at elucidating the impact of PAL on autophagic processes and exploring the potential of combining it with trametinib (TRA), an MEK inhibitor, our research seeks to address the challenge of PAL-induced drug resistance. Our findings reveal that PAL significantly decreases the viability of MCF7 and MDA-MB-468 cells and reduces tumor size in mice while showing minimal cytotoxicity in MCF10A cells. However, PAL also induces protective autophagy, potentially leading to drug resistance via the RAF/MEK/ERK pathway activation. Introducing TRA effectively neutralized this autophagy, enhancing PAL's anti-tumor efficacy. A combination of PAL and TRA synergistically reduced cell viability and proliferation, and in vivo studies showed notable tumor size reduction. In conclusion, the PAL and TRA combination emerges as a promising strategy for overcoming PAL-induced resistance, offering a new horizon in breast cancer treatment. [ABSTRACT FROM AUTHOR]

To overcome the drug resistance in MCF7 cancer cells and enhance their sensitivity to cisplatin, a liposomal (Lip) nanocarrier modified by arginine-glycine-aspartic acid (RGD) to co-deliver cisplatin (Cis) and miRNA biomolecule (miR-34a) was investigated. The efficiency of this nanocarrier was evaluated through in vitro and in vivo assays against MCF7 and 4T1 cells, respectively. The in vitro results demonstrated that the miR34a-Cis-Lip-RGD formulation had significantly higher efficiency and also a higher apoptotic effect compared to both miR34a-Cis and miR34a-Cis-Lip (76.24%, 58.29%, and 56.2%, respectively). Additionally, miR34a-Cis-Lip exhibited an overall CI value below 1, indicating a synergistic effect of Cis and miR-34a within the Lip system. The miR34a-Cis-Lip-RGD increased the Bax gene expressions compared to both miR34a-Cis-Lip and Cis-miR34a, possibly due to the integrin receptors on the cells, leading to higher uptake. The efficiency of miR34a-Cis-Lip-RGD in reducing tumor size was significantly higher than Cis-miR34a and miR34a-Cis-Lip. The lower volume of the tumor in the group treated with Cis-miR34a-Lip-RGD is presumed to be attributed to improved cellular uptake facilitated by the RGD modification, which enhances the targeted delivery of the therapeutic payload to cancer cells. The overall weight of the mice in all the groups did not exhibit significant changes. This consistent weight maintenance implies the safety of the designed delivery system for vital organs, indicating that the designed delivery system may offer a promising solution to minimize unwanted side effects associated with conventional cancer treatments. [ABSTRACT FROM AUTHOR]

Breast cancer is the second leading cause of death among women, and the number of mortal cases in diagnosed patients is constantly increasing. The search for new plant compounds with antitumor effects is very important because of the side effects of conventional therapy and the development of drug resistance in cancer cells. The use of plant substances in medicine has been well known for centuries, but the exact mechanism of their action is far from being elucidated. The molecular mechanisms of cytotoxicity exerted by secondary metabolites and bioactive peptides of plant origin on breast cancer cell lines are the subject of this review. [ABSTRACT FROM AUTHOR]

Acanthospermum hispidum DC (Asteraceae), a traditional medicinal plant, plays a role as an alternative remedy for various diseases, such as bacterial and viral infections, jaundice, malaria, fever, gastrointestinal disorders, headache, convulsions, and snake bites. Flavonoids, alkaloids, saponins, tannins, terpenes, steroids, and cardioactive glycosides are the distinct classes of metabolites in the plant. Although A. hispidum was suggested as a promising antitumor phytomedicine, no studies identified its potential cytotoxic components. In this study, the cytotoxic compounds of A. hispidum were isolated using chromatographic techniques guided by in vitro MTT cytotoxicity assay against selected cancer cell lines; breast cancer (MCF7), colorectal adenocarcinoma (HT29), and hepatoblastoma (HepG2). The selective index (SI) was assessed on MRC5 (Normal human fetal lung fibroblast) cell line. The dichloromethane fraction (DCM) showed remarkable cytotoxic activity against MCF7 and HT29 (%Cell viability; 46.15 and 60.5, respectively). Hence, the main bioactive fraction from DCM was purified to afford two phytosterols; stigmasterol (1) and β-sitosterol (2), which were identified by 1-D and 2-D NMR spectroscopy. Cytotoxic evaluation of 1 and 2 revealed that β-sitosterol showed better selective cytotoxicity against MCF7 and HT29 (IC50 4.07 μg/mL, SI 2.63; IC50 4.52 μg/mL, SI 2.37) compared to stigmasterol (IC50 5.43 μg/mL, SI 1.38; IC50 4.21 μg/mL, SI 1.78), respectively. Bioinformatic assessments of drug-likeness and ADMET properties demonstrated that most criteria were obeyed by the investigated compounds except for their poor solubility, which recommended the preparation of special dosage forms, such as nanoformulation to enhance their oral bioavailability. Swiss Target prediction indicated that nuclear receptors represent the main target class (40%). Whereas caspase-3 stimulant activity (a key enzyme in apoptosis) was predicted by the PASS prediction tool as a potential anticancer mechanism. Our study suggests A. hispidum as a potential source of bioactive phytosterols and as a chemopreventive medicinal plant.

Abstract To overcome the drug resistance in MCF7 cancer cells and enhance their sensitivity to cisplatin, a liposomal (Lip) nanocarrier modified by arginine-glycine-aspartic acid (RGD) to co-deliver cisplatin (Cis) and miRNA biomolecule (miR-34a) was investigated. The efficiency of this nanocarrier was evaluated through in vitro and in vivo assays against MCF7 and 4T1 cells, respectively. The in vitro results demonstrated that the miR34a-Cis-Lip-RGD formulation had significantly higher efficiency and also a higher apoptotic effect compared to both miR34a-Cis and miR34a-Cis-Lip (76.24%, 58.29%, and 56.2%, respectively). Additionally, miR34a-Cis-Lip exhibited an overall CI value below 1, indicating a synergistic effect of Cis and miR-34a within the Lip system. The miR34a-Cis-Lip-RGD increased the Bax gene expressions compared to both miR34a-Cis-Lip and Cis-miR34a, possibly due to the integrin receptors on the cells, leading to higher uptake. The efficiency of miR34a-Cis-Lip-RGD in reducing tumor size was significantly higher than Cis-miR34a and miR34a-Cis-Lip. The lower volume of the tumor in the group treated with Cis-miR34a-Lip-RGD is presumed to be attributed to improved cellular uptake facilitated by the RGD modification, which enhances the targeted delivery of the therapeutic payload to cancer cells. The overall weight of the mice in all the groups did not exhibit significant changes. This consistent weight maintenance implies the safety of the designed delivery system for vital organs, indicating that the designed delivery system may offer a promising solution to minimize unwanted side effects associated with conventional cancer treatments.

Purpose: Nanotechnology creates materials for medical purposes, such as nanocarriers or smart polymers that target and treat diseases like cancer. Methods: In this study, hybrid carriers based on doxorubicin/poly(N-vinylcaprolactam) (DOX-PVCL) and doxorubicin-loaded niosome /poly(N-vinylcaprolactam) (DOX-Nio-PVCL) have been constructed as thermoresponsive polymers. At first, PVCL was synthesized and purified. Then, the DOX-Nio was prepared by the thin layer evaporation method and loaded into the PVCL. Furthermore, doxorubicin was loaded on PVCL by the same method. The structure features and morphology of the synthesized particles were determined using Fourier-transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR), Raman spectroscopy, and electron microscopy. The synthesized particles’ size was measured at 25˚C and 37˚C by dynamic light scattering (DLS). Results: The lower critical solution temperature (LCST) was determined and showed 32.5, 28.5, 28.5 ˚C values for PVCL, DOX-Nio-PVCl, and DOX-PVCL dissolved in phosphate-buffered saline, respectively. The release behavior of doxorubicin showed that the synthesized formulations had more potential release at pH 5.5 than pH 7.4. Evaluation of the cytotoxicity of PVCL on MCF-7 did not show any significant toxicity for concentrations 5.8–29 µg/mL. MCF-7 cell viability was investigated in the presence of DOX, DOX-Nio, DOX-Nio-PVCL, and DOX-PVCL at a final concentration of 29 µg/mL and 1.1 µg/mL of polymer and drug, respectively. Our results showed the highest MCF-7 cell death in DOX-PVCL-treated cells. Conclusion: While the synthetic polymer displayed promising abilities in eliminating cancer cells, further study is necessary to explore its potential as a medicinal treatment, particularly in understanding its impact on in vivo structures. [ABSTRACT FROM AUTHOR]

Curcumin plays a leading role as an epigenetic regulator in cancer. miR-15a-5p is a crucial non-coding RNA for breast cancer (BRCA) and various cancers due to its tumor suppressor role. In our study, we aimed to examine the curcumin/miR-15a-5p/target gene interaction in BRCA cells.

Background: Transforming growth factor beta (TGFβ) is important for the morphogenesis and secretory function of the mammary gland. It is one of the main activators of the epithelial–mesenchymal transition (EMT), a process important for tissue remodeling and regeneration. It also provides cells with the plasticity to form metastases during tumor progression. Noncancerous and cancer cells respond differently to TGFβ. However, knowledge of the cellular signaling cascades triggered by TGFβ in various cell types is still limited. Methods: MCF10A (noncancerous, originating from fibrotic breast tissue) and MCF7 (cancer, estrogen receptor-positive) breast epithelial cells were treated with TGFB1 directly or through conditioned media from stimulated cells. Transcriptional changes (via RNA-seq) were assessed in untreated cells and after 1–6 days of treatment. Differentially expressed genes were detected with DESeq2 and the hallmark collection was selected for gene set enrichment analysis. Results: TGFB1 induces EMT in both the MCF10A and MCF7 cell lines but via slightly different mechanisms (signaling through SMAD3 is more active in MCF7 cells). Many EMT-related genes are expressed in MCF10A cells at baseline. Both cell lines respond to TGFB1 by decreasing the expression of genes involved in cell proliferation: through the repression of MYC (and the protein targets) in MCF10A cells and the activation of p63-dependent signaling in MCF7 cells (CDKN1A and CDKN2B, which are responsible for the inhibition of cyclin-dependent kinases, are upregulated). In addition, estrogen receptor signaling is inhibited and caspase-dependent cell death is induced only in MCF7 cells. Direct incubation with TGFB1 and treatment of cells with conditioned media similarly affected transcriptional profiles. However, TGFB1-induced protein secretion is more pronounced in MCF10A cells; therefore, the signaling is propagated through conditioned media (bystander effect) more effectively in MCF10A cells than in MCF7 cells. Conclusions: Estrogen receptor-positive breast cancer patients may benefit from high levels of TGFB1 expression due to the repression of estrogen receptor signaling, inhibition of proliferation, and induction of apoptosis in cancer cells. However, some TGFB1-stimulated cells may undergo EMT, which increases the risk of metastasis. Plain English summary: Transforming growth factor beta (TGFβ) is a multifaceted cytokine that controls numerous physiological and pathological processes during development and carcinogenesis. Its best-known function is the activation of epithelial–mesenchymal transition (EMT), a process crucial for tissue remodeling and regeneration. During EMT, epithelial cells lose their connections to adjacent cells and acquire mesenchymal characteristics, such as migratory ability. Compared with cancer cells, normal (nontumorigenic) cells usually respond differently to TGFβ stimulation. Typically, TGFβ inhibits the proliferation of epithelial cells and may promote cell death. In cancer cells, TGFβ often promotes tumor progression. TheTGFβ-mediated induction of EMT increases cell mobility, which is associated with the formation of metastases and tumor invasion. In this work, we compared the transcriptional response of noncancerous (MCF10A) and cancerous (MCF7; estrogen receptor-positive) breast epithelial cells to direct stimulation by TGFB1 and its indirect effect through conditioned media. Some of TGFB1-induced changes, including inhibition of proliferation and induction of EMT, were similar in both cell lines. However, these changes were associated with different upstream signaling pathways. Other changes were more specific, such as disruption of estrogen-related signaling or induction of cell death in MCF7 cells. Direct incubation with TGFB1 and treatment of cells with conditioned media similarly affected target cells, indicating the presence of a bystander effect. Moreover, transcript profiling by RNA-seq revealed that the TGFβ signaling pathway is already active in untreated MCF10A cells, which may be due to their origination from a fibrotic lesion. [ABSTRACT FROM AUTHOR]

Chalcone derivatives have been proven and documented as non-steroidal anticancer agents. A study of chalcone can be performed as an aromatase inhibitor. One crucial strategy for managing estrogen-positive breast cancer is aromatase inhibition. A total of 13 derivatives of chalcone were synthesized by the aldol condensation reaction and characterized by FTIR, MS, and NMR. Molecular docking was performed by the maestro Schrodinger Suite. In silico ADME study was executed by the QikProp software. All 13 compounds were assessed for the cytotoxicity study in human cancer cell line MCF-7 and are subject to further aromatase inhibition assay on selected chalcone derivatives. Four compounds, 3gA, 3jA, 3kA, and 3lA were found to be more potent chalcone derivatives with their IC50 values of 18.13±1.19 µM, 21.71±1.61 µM, 16.36±1.47 µM and 21.06±1.87 µM, respectively. Using a fluorogenic test kit, the in vitro aromatase inhibitory activity of four drugs (3gA, 3jA, 3kA, and 3lA) was investigated. The values of IC50 for compounds 3gA, 3jA, 3kA, and 3lA were found to be 2.76±0.83 µM, 6.45±3.38 µM, 4.82±1.52 µM and 3.00±1.63 µM, respectively. Lastly, QikProp 4.8 software was used to calculate the ADME parameters (absorption, distribution, metabolism, and excretion) of synthesized compounds. It was concluded that 3gA is the most potent compound having potent aromatase inhibitory activity in comparison to Letrozole with an IC50 value of 2.76±0.83 µM. At the same time, 3jA and 3lA have good aromatase inhibitory activity. Therefore, For the identification of aromatase inhibitory activity, these compounds make good lead compounds for further study as anticancer agents. [ABSTRACT FROM AUTHOR]

Rosuvastatin (ROS), a statin drug with promising anticancer properties has a low bioavailability of approximately 20% due to lipophilicity and first-pass metabolism. This study aimed to enhance ROS anticancer efficacy through loading into flexible chitosomes. The chitosomes were prepared starting from negatively charged liposomes through electrostatic interactions with chitosan. The conversion of zeta potential from negative to positive confirmed the successful formation of chitosomes. The chitosan coating increased the particle size and zeta potential, which ranged from 202.0 ± 1.7 nm to 504.7 ± 25.0 nm and from − 44.9 ± 3.0 mV to 50.1 ± 2.6 mV, respectively. Chitosan and drug concentrations had an important influence on the chitosome properties. The optimum chitosome formulation was used to prepare ROS-loaded flexible chitosomes using different concentrations of four edge activators. The type and concentration of edge activator influenced the particle size, drug entrapment efficiency, and drug release rate of the flexible chitosomes. Flexible chitosomes significantly increased drug permeation through rat abdominal skin compared to control transferosomes and drug solution. The optimal ROS flexible chitosomes containing sodium deoxycholate as an edge activator had a 2.23-fold increase in ROS cytotoxic efficacy against MCF7 cells and a 1.84-fold increase against HepG2 cells. These results underscore the potential of flexible chitosomes for enhancing ROS anticancer efficacy. [ABSTRACT FROM AUTHOR]

Metformin is commonly prescribed to people with diabetes. Metformin has been shown in previous studies to be able to prevent the growth of cancer cells. This study aims to investigate the effects of metformin and gold nanoparticles in MCF7 breast cancer and A549 lung cell lines. The effects of metformin and gold nanoparticles on MCF7 breast cancer and A549 lung cells were determined on cells grown in 24 h cell culture. MCF-7 and A549 cells were incubated for 24 h with the treatment of escalating molar concentrations of ifosfamide. The MTT assay was used to determine the cytotoxicity of metformin toward MCF7 and A549 cell lines. The expression of Bax, BCL2, PI3K, Akt3, mTOR, Hsp60, Hsp70, and TNF-α was measured by RT-PCR. Metformin and gold nanoparticles inhibited the proliferation of MCF-7 and A549 cells in a dose and time-dependent manner with an IC50 value of 5 µM and 10 µg/mL. RT-PCR assays showed ifosfamide + metformin + gold nanoparticles significantly reduced the expression of BCL2, PI3K, Akt3, mTOR, Hsp60 and Hsp70 and increased the expression of TNF-α and Bax. The findings obtained in this study suggest that further studies should be conducted, and metformin and gold nanoparticles can be used in breast cancer and lung cancer treatments. [ABSTRACT FROM AUTHOR]

Zinc oxide nanoparticles (ZnO-NPs) are metal oxide NPs that have high cytotoxicity on cancer cells and low cytotoxicity on healthy cells. Breast cancer is the most frequent type of cancer-causing death among women worldwide. In this study, anti-cancer effects of ZnO-NPs were investigated. For this purpose, we treated the MCF7 and MDA-MB-231 breast cancer cell lines and human umbilical vein endothelial cells HUVEC cell line with 10 μg/mL and 20 μg/mL ZnO-NP. Anti-cancer effects of ZnO-NPs were evaluated with cell viability, apoptotic index and colony formation assays, and anti-Warburg effect were investigated by evaluating of pyruvate dehydrogenase (PDH) and Lactate Dehydrogenase A (LDHA) protein expressions. Results indicated that, ZnO-NP application did not have a cytotoxic effect on HUVEC cells, it had cytotoxicity on both breast cancer cell lines. However, MCF7 cells were more sensitive to ZnO-NP treatment. Administration of 20 μg/mL ZnO-NP reduced the survival of MCF7 cells by 62% and increased the apoptotic index by approximately 6 times. Additionally, ZnO-NP treatment inhibited the doubling times of cells and suppressed the colony-forming abilities of both breast cancer cell lines. Also, it was seen that ZnO-NP treatment increased PDH expression in MCF7 cells, where the apoptotic index was more induced. As a result, we have shown for the first time that ZnO-NPs affect the energy metabolism of cells by increasing PDH expression in MCF7 cells, thus increasing the apoptotic index. Our study, which observed the anticancer effects of ZnO-NPs on breast cancer cells, will also shed light on future experimental studies.

Abstract Background The ketogenic diet (KD), based on high fat (over 70% of daily calories), low carbohydrate, and adequate protein intake, has become popular due to its potential therapeutic benefits for several diseases including cancer. Under KD and starvation conditions, the lack of carbohydrates promotes the production of ketone bodies (KB) from fats by the liver as an alternative source of metabolic energy. KD and starvation may affect the metabolism in cancer cells, as well as tumor characteristics. The aim of this study is to evaluate the effect of KD conditions on a wide variety of aspects of breast cancer cells in vitro. Methods Using two cancer and one non-cancer breast cell line, we evaluate the effect of β-hydroxybutyrate (βHb) treatment on cell growth, survival, proliferation, colony formation, and migration. We also assess the effect of KB on metabolic profile of the cells. Using RNAseq analysis, we elucidate the effect of βHb on the gene expression profile. Results Significant effects were observed following treatment by βHb which include effects on viability, proliferation, and colony formation of MCF7 cells, and different effects on colony formation of MDA-MB-231 cells, with no such effects on non-cancer HB2 cells. We found no changes in glucose intake or lactate output following βHb treatment as measured by LC-MS, but an increase in reactive oxygen species (ROS) level was detected. RNAseq analysis demonstrated significant changes in genes involved in lipid metabolism, cancer, and oxidative phosphorylation. Conclusions Based on our results, we conclude that differential response of cancer cell lines to βHb treatment, as alternative energy source or signal to alter lipid metabolism and oncogenicity, supports the need for a personalized approach to breast cancer patient treatment.

Zinc oxide nanoparticles (ZnO-NPs) are metal oxide NPs that have high cytotoxicity on cancer cells and low cytotoxicity on healthy cells. Breast cancer is the most frequent type of cancer-causing death among women worldwide. In this study, anti-cancer effects of ZnO-NPs were investigated. For this purpose, we treated the MCF7 and MDA-MB-231 breast cancer cell lines and human umbilical vein endothelial cells HUVEC cell line with 10 μg/mL and 20 μg/mL ZnO-NP. Anti-cancer effects of ZnO-NPs were evaluated with cell viability, apoptotic index and colony formation assays, and anti-Warburg effect were investigated by evaluating of pyruvate dehydrogenase (PDH) and Lactate Dehydrogenase A (LDHA) protein expressions. Results indicated that, ZnO-NP application did not have a cytotoxic effect on HUVEC cells, it had cytotoxicity on both breast cancer cell lines. However, MCF7 cells were more sensitive to ZnO-NP treatment. Administration of 20 μg/mL ZnO-NP reduced the survival of MCF7 cells by 62% and increased the apoptotic index by approximately 6 times. Additionally, ZnO-NP treatment inhibited the doubling times of cells and suppressed the colony-forming abilities of both breast cancer cell lines. Also, it was seen that ZnO-NP treatment increased PDH expression in MCF7 cells, where the apoptotic index was more induced. As a result, we have shown for the first time that ZnO-NPs affect the energy metabolism of cells by increasing PDH expression in MCF7 cells, thus increasing the apoptotic index. Our study, which observed the anticancer effects of ZnO-NPs on breast cancer cells, will also shed light on future experimental studies. [ABSTRACT FROM AUTHOR]

Background: The ketogenic diet (KD), based on high fat (over 70% of daily calories), low carbohydrate, and adequate protein intake, has become popular due to its potential therapeutic benefits for several diseases including cancer. Under KD and starvation conditions, the lack of carbohydrates promotes the production of ketone bodies (KB) from fats by the liver as an alternative source of metabolic energy. KD and starvation may affect the metabolism in cancer cells, as well as tumor characteristics. The aim of this study is to evaluate the effect of KD conditions on a wide variety of aspects of breast cancer cells in vitro. Methods: Using two cancer and one non-cancer breast cell line, we evaluate the effect of β-hydroxybutyrate (βHb) treatment on cell growth, survival, proliferation, colony formation, and migration. We also assess the effect of KB on metabolic profile of the cells. Using RNAseq analysis, we elucidate the effect of βHb on the gene expression profile. Results: Significant effects were observed following treatment by βHb which include effects on viability, proliferation, and colony formation of MCF7 cells, and different effects on colony formation of MDA-MB-231 cells, with no such effects on non-cancer HB2 cells. We found no changes in glucose intake or lactate output following βHb treatment as measured by LC-MS, but an increase in reactive oxygen species (ROS) level was detected. RNAseq analysis demonstrated significant changes in genes involved in lipid metabolism, cancer, and oxidative phosphorylation. Conclusions: Based on our results, we conclude that differential response of cancer cell lines to βHb treatment, as alternative energy source or signal to alter lipid metabolism and oncogenicity, supports the need for a personalized approach to breast cancer patient treatment. [ABSTRACT FROM AUTHOR]

Breast cancer is an issue of concern with increasing incidence among women worldwide. Propranolol, as an antihypertensive drug, exerts anticancer effects too. We conducted this study to analyze the in vitro apoptotic and antiproliferative effects of propranolol in human MCF-7 breast cancer cells. MCF-7 cells were seeded into 6-well plates and treated with 50 µL propranolol for 24 hours. After cell homogenization, the levels of pro-apoptotic proteins BCL2 associated X (BAX), apoptosis inducing factor (AIF), C/-EBP homologous protein (GADD153), and glucose-regulated protein 78 (GRP78), anti-apoptotic protein BCL2 apoptosis regulator (BCL-2), and cycle-regulator WEE1 G2 checkpoint kinase (WEE1) were measured with ELISA. Propranolol significantly upregulated pro-apoptotic proteins AIF, BAX, GADD153, and GRP78 while downregulated anti-apoptotic protein BCL2. The level of WEE1, as the main regulatory cell cycle protein at the G2/M checkpoint, significantly increased after propranolol treatment. Propranolol inhibited the proliferation of MCF-7 human breast cancer cells by upregulating pro-apoptotic factors AIF, BAX, GADD153 and GRP78 and by downregulating antiapoptotic BCL2. Elevated WEE1 levels after propranolol treatment might lead the tumor cells into a sustained cell-cycle arrest which eventually resulted in caspase-dependent or -independent mitochondrial or endoplasmic-reticulum stress-induced apoptosis. So, propranolol can be utilized as a potential therapeutic agent in breast cancer therapy. [ABSTRACT FROM AUTHOR]

Breast cancer is the second leading cause of death among women, and the number of mortal cases in diagnosed patients is constantly increasing. The search for new plant compounds with antitumor effects is very important because of the side effects of conventional therapy and the development of drug resistance in cancer cells. The use of plant substances in medicine has been well known for centuries, but the exact mechanism of their action is far from being elucidated. The molecular mechanisms of cytotoxicity exerted by secondary metabolites and bioactive peptides of plant origin on breast cancer cell lines are the subject of this review.

The study synthesized Pluronic F-127 nanoparticles that encapsulate Fe2O3 (PF127Fe2O3NPs), nanoparticles, characterized their formation, and evaluated their cytotoxicity and anticancer activity using Berberis vulgaris leaf extract, using various analytical methods such as FTIR, Ultraviolet-visible, photoluminescence, dynamic light scattering, X-ray diffraction, and morphology analysis. We assessed the antioxidant properties of PF127Fe2O3NPs, cytotoxicity, and apoptosis through 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay and acridine orange/ethidium bromide staining in breast cancer cells, such as MCF7, and MDA-MB-231. The characterization results demonstrated that PF-127 was coated with Fe2O3 nanoparticles. MTT assay data revealed that PF127Fe2O3NPs effectively prevent cancer cells from proliferating and act as an anticancer drug. The antimicrobial results revealed that the fabricated nanoparticles are effective against gram-negative (Klebsiella pneumoniae, Escherichia coli, and Shigella dysenteriae) and gram-positive (Streptococcus pneumoniae, Staphylococcus aureus, and Bacillus subtilis) bacteria. Treatment of PF127Fe2O3NPs in a dose-dependent manner on MCF7, and MDA-MB-231, exhibited increased antioxidant activity, nuclear damage, and apoptotic activity. These results confirm the apoptotic activity of PF127Fe2O3NPs. The study concludes that MCF7 appears to be more sensitive to PF127Fe2O3NPs than MDA-MB-231. In conclusion, we have found that it can be used as an effective antioxidant and anticancer agent in therapeutics.

Tarek A Ahmed,1 Ehab MM Ali,2 Abdelsattar M Omar,3 Alshaimaa M Almehmady,1 Khalid M El‐Say1 1Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Kingdom of Saudi Arabia; 2Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, 21589, Kingdom of Saudi Arabia; 3Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Kingdom of Saudi ArabiaCorrespondence: Tarek A Ahmed, Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, 21589, Kingdom of Saudi Arabia, Tel +966 2 640 0000 Ext 22250, Email tabdelnapy@kau.edu.saBackground: Ezetimibe, initially recognized as a cholesterol-lowering agent, has recently attracted attention due to its potential anticancer properties. We aimed to explore an innovative approach of enhancing the drug anticancer activity through the development of drug nano-formulations.Materials and Methods: Fifteen different nano-micelles formulations were prepared utilizing D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and pluronic F127. The prepared formulations were characterized for size, polydispersity index (PDI), zeta potential, and entrapment efficiency (EE). The formulations were morphologically characterized using light and transmission electron microscopies and the drug-binding mode with the active site was investigated using the molecular docking. Cell viability against MCF-7 and T47D was studied. Apoptosis and cell cycle were assessed.Results: The prepared formulations were in the nano-size range (34.01 ± 2.00– 278.34 ± 9.11 nm), zeta potential values were very close to zero, and the TPGS-based micelles formulations showed the highest ezetimibe EE (94.03 ± 1.71%). Morphological study illustrated a well-defined, spherical nanoparticles with a uniform size distribution. Molecular docking demonstrated good interaction of ezetimibe with Interleukin-1 Beta Convertase through multiple hydrogen bonding, covalent bond, and hydrophobic interaction. TPGS-based nano-micelle formulation (F5) demonstrated the lowest IC50 against MCF-7 (4.51 μg/mL) and T47D (8.22 μg/mL) cancer cells. When T47D cells were treated with IC50 concentrations of F5, it exhibited significant inhibition with late apoptosis (43.9%), a response comparable to T47D cells treated with an IC50 dose of ezetimibe. Cell cycle analysis revealed that both ezetimibe and F5-treated T47D cells exhibited an increase in the subG1 phase, indicating reduced DNA content and cell death.Conclusion: These findings suggest that F5 could serve as a proficient drug delivery system in augmenting the cytotoxic activity of ezetimibe against breast cancer.Keywords: ezetimibe, TPGS, pluronic, micelles, anticancer activity, MCF7, T47D

Purpose: Eliminating cancer stem cells (CSCs) is a challenge because of their enhanced resistance to anti-cancer drugs. Vitamin C, which is insufficient in patients with higher stages of cancer, has been gaining attention as a potential treatment for human malignancies. Hence this study aimed to analyze the effect of high-dose vitamin C treatment on the gene expression level of HIF-1α, NF-κB1, BAX, and DNMT1 in the MCF7 cells undergoing hypoxia, as an inducer of CSCs characteristics. As a result, vitamin C could be possibly used as a promising therapeutic adjuvant. Methods: Here we first analyzed the breast CSC population alteration in MCF7 cells following hypoxia induction. Then, we evaluated the impact of vitamin C treatment on the gene expression level of four stemness-related genes in hypoxic MCF7 cells. Results: Our results indicate that vitamin C could reduce proliferation and stemness states in CSCs possibly by induction of apoptotic markers such as BAX, along with attenuating stemness markers, including NF-κB1, and DNMT1 gene expressions. Conclusion: According to our findings, vitamin C administration would become a new approach to avoiding the stimulation of CSCs during cancer therapies.

Purpose: Estrogen Receptor α (ERα) is a well-established therapeutic target for Estrogen Receptor (ER)-positive breast cancers. Both Selective Estrogen Receptor Degraders (SERD) and PROTAC ER degraders are synthetic compounds suppressing the ER activity through the degradation of ER. However, the differences between SERD and PROTAC ER degraders are far from clear. Methods: The effect of PROTAC ER degrader ERD-148 and SERD fulvestrant on protein degradation was evaluated by western blot analysis. The cell proliferation was tested by WST-8 assays and the gene expressions were assessed by gene microarray and real-time RT-PCR analysis after the compound treatment. Results: ERD-148 is a potent and selective PROTAC ERα degrader. It degrades not only unphosphorylated ERα but also the phosphorylated ERα in the cells. In contrast, the SERD fulvestrant showed much-reduced degradation potency on the phosphorylated ERα. The more complete degradation of ERα by ERD-148 translates into a greater maximum cell growth inhibition. However, ERD-148 and fulvestrant share a similar gene regulation profile except for the variation of regulation potency. Further studies indicate that ERD-148 degrades the ERα in fulvestrant-resistant cells. Conclusion: PROTAC ER degrader has a different mechanism of action compared to SERD which may be used in treating fulvestrant-resistant cancers. [ABSTRACT FROM AUTHOR]

Ashwagandha (Withania somnifera) has gained worldwide popularity for a multitude of health benefits inclusive of cancer-preventive and curative effects. Despite numerous research data supporting the benefits of this wonder herb, the actual use of ashwagandha for cancer treatment in clinics is limited. The primary reason for this is the inconsistent therapeutic outcome due to highly variable composition and constitution of active ingredients in the plant extract impacting ashwagandha's pharmacology. We investigate here an engineered yield: an ashwagandha extract (Oncowithanib) that has a unique and fixed portion of active ingredients to achieve consistent and effective therapeutic activity. Using the MCF7 cell line, Oncowithanib was studied for its anti-neoplastic efficacy and drug targets associated with cell cycle regulation, translation machinery, and cell survival and apoptosis. Results demonstrate a dose-dependent decline in Oncowithanib-treated MCF7 cell viability and reduced colony-forming ability. Treated cells showed increased cell death as evidenced by enhancement of Caspase 3 enzyme activity and decreased expressions of cell proliferation markers such as Ki67 and Aurora Kinase A. Oncowithanib treatment was also found to be associated with expressional suppression of key cellular kinases such as RSK1, Akt1, and mTOR in MCF7 cells. Our findings indicate that Oncowithanib decreases MCF7 cell survival and propagation, and sheds light on common drug targets that might be good candidates for the development of cancer therapeutics. Further in-depth investigations are required to fully explore the potency and pharmacology of this novel extract. This study also highlights the importance of the standardization of herbal extracts to get consistent therapeutic activity for the disease indication. [ABSTRACT FROM AUTHOR]

Methotrexate, a folic acid molecular alternative inhibiting dihydrofolate reductase (DHFR), is employed for the treatment of various types of tumors combined with aspirin; acetylsalicylic acid is a nonsteroidal anti-inflammatory drug (NSAID). The present study aimed to detect the combined effects of both medications on MCF7 cell line activity. The drug combinations of aspirin and methotrexate were tested for cytotoxicity against the breast cancer cell line MCF7 using the MTT assay. The results showed that methotrexate, aspirin, and combination drugs have potent cytotoxicity against MCF7 cells. The mean IC50 of the methotrexate-treated group was 155.7 µg/ml (range, 77.89 to 311µg/ml. However, the IC50 of the aspirin-treated group was 465 µg/ml (range, 243.3 to 888.6 µg/ml). The IC50 of combination drugs used in the CompuSyn Isobologram on MCF7 cell lines, the cytotoxicity of medications methotrexate, aspirin, and combination demonstrated a synergistic action, and combination drugs have potent cytotoxicity against MCF7 cell lines. In conclusion, the combination of methotrexate and aspirin has a potent anticancer effect. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common cancer among women. Epidemiologists estimate that over 2.3 million new cases of breast cancer are diagnosed worldwide each year. Natural compounds represent promising molecules for the development of antitumor drugs; among them, lignans show significant antiproliferative effects against breast cancer cells. The goal of the study was to analyse the antiproliferative effects of lignan honokiol on MCF7 breast cancer cells, find synergistic combinations of honokiol with 2-deoxyglucose, and evaluate the effects of the combinations found on cells in hypoxia. The antiproliferative effects of the compounds were evaluated by the MTT test, and protein expression analysis was performed by immunoblotting. Honokiol inhibited MCF7 cell growth with an IC50 value of 19.7 μM. Synergistic combinations of honokiol with the glycolysis inhibitor 2-deoxyglucose were detected; the compounds at low doses caused significant suppression of MCF7 cell growth. The established combinations of compounds inhibited HIF-1α expression and were effective in hypoxia, considered as the leading factor of chemotherapeutic resistance. Oestrogen receptor alpha (ERα) is the main growth driver of hormone-dependent breast tumours. Honokiol combined with 2-deoxyglucose reduced ERα expression in MCF7 cells, and expression of the hormone-dependent protein GREB1 was also downregulated. Honokiol at a concentration of 15 μM in combination with 6 mM 2-deoxyglucose induced the cleavage of PARP (a marker of apoptosis) in MCF7 cells after 48 h of incubation. The cells treated with the combination of honokiol and 2-deoxyglucose demonstrated a decrease in the expression of cyclin D1. Thus, honokiol represents a promising basis for the development of antitumor agents; the combination of this natural compound with glycolysis inhibitors can be used to reduce the applied doses. [ABSTRACT FROM AUTHOR]

According to data provided by the World Health Organization (WHO), a total of 2.3 million women across the globe received a diagnosis of breast cancer in the year 2020, and among these cases, 685,000 resulted in fatalities. As the incidence of breast cancer statistics continues to rise, it is imperative to explore new avenues in the ongoing battle against this disease. Therefore, a number of new indolyl-hydrazones were synthesized by reacting the ethyl 3-formyl-1H-indole-2-carboxylate 1 with thiosemicarbazide, semicarbazide.HCl, 4-nitrophenyl hydrazine, 2,4-dinitrophenyl hydrazine, and 4-amino-5-(1H-indol-2-yl)-1,2,4-triazole-3-thione to afford the new hit compounds, which were assigned chemical structures as thiosemicarbazone 3, bis(hydrazine derivative) 5, semicarbzone 6, Schiff base 8, and the corresponding hydrazones 10 and 12 by NMR, elemental analysis, and X-ray single-crystal analysis. The MTT assay was employed to investigate the compounds' cytotoxicity against breast cancer cells (MCF-7). Cytotoxicity results disclosed potent IC50 values against MCF-7, especially compounds 5, 8, and 12, with IC50 values of 2.73 ± 0.14, 4.38 ± 0.23, and 7.03 ± 0.37 μM, respectively, compared to staurosproine (IC50 = 8.32 ± 0.43 μM). Consequently, the activities of compounds 5, 8, and 12 in relation to cell migration were investigated using the wound-healing test. The findings revealed notable wound-healing efficacy, with respective percentages of wound closure measured at 48.8%, 60.7%, and 51.8%. The impact of the hit compounds on cell proliferation was assessed by examining their apoptosis-inducing properties. Intriguingly, compound 5 exhibited a significant enhancement in cell death within MCF-7 cells, registering a notable increase of 39.26% in comparison to the untreated control group, which demonstrated only 1.27% cell death. Furthermore, the mechanism of action of compound 5 was scrutinized through testing against kinase receptors. The results revealed significant kinase inhibition, particularly against PI3K-α, PI3K-β, PI3K-δ, CDK2, AKT-1, and EGFR, showcasing promising activity, compared to standard drugs targeting these receptors. In the conclusive phase, through in vivo assay, compound 5 demonstrated a substantial reduction in tumor volume, decreasing from 106 mm³ in the untreated control to 56.4 mm³. Moreover, it significantly attenuated tumor proliferation by 46.9%. In view of these findings, the identified leads exhibit promises for potential development into future medications for the treatment of breast cancer, as they effectively hinder both cell migration and proliferation. [ABSTRACT FROM AUTHOR]

The identification of new cancer-associated genes/proteins, the characterization of their expression variation, the interactomics-based assessment of differentially expressed genes/proteins (DEGs/DEPs), and understanding the tumorigenic pathways and biological processes involved in BC genesis and progression are necessary and possible by the rapid and recent advances in bioinformatics and molecular profiling strategies. Taking into account the opinion of other authors, as well as based on our own team's in vitro studies, we suggest that the human jumping translocation breakpoint (hJTB) protein might be considered as a tumor biomarker for BC and should be studied as a target for BC therapy. In this study, we identify DEPs, carcinogenic pathways, and biological processes associated with JTB silencing, using 2D-PAGE coupled with nano-liquid chromatography tandem mass spectrometry (nLC-MS/MS) proteomics applied to a MCF7 breast cancer cell line, for complementing and completing our previous results based on SDS-PAGE, as well as in-solution proteomics of MCF7 cells transfected for JTB downregulation. The functions of significant DEPs are analyzed using GSEA and KEGG analyses. Almost all DEPs exert pro-tumorigenic effects in the JTBlow condition, sustaining the tumor suppressive function of JTB. Thus, the identified DEPs are involved in several signaling and metabolic pathways that play pro-tumorigenic roles: EMT, ERK/MAPK, PI3K/AKT, Wnt/β-catenin, mTOR, C-MYC, NF-κB, IFN-γ and IFN-α responses, UPR, and glycolysis/gluconeogenesis. These pathways sustain cancer cell growth, adhesion, survival, proliferation, invasion, metastasis, resistance to apoptosis, tight junctions and cytoskeleton reorganization, the maintenance of stemness, metabolic reprogramming, survival in a hostile environment, and sustain a poor clinical outcome. In conclusion, JTB silencing might increase the neoplastic phenotype and behavior of the MCF7 BC cell line. The data is available via ProteomeXchange with the identifier PXD046265. [ABSTRACT FROM AUTHOR]

The number of deaths due to malignant neoplasms is increasing year by year. For this reason, new ways of preventing them and supporting treatment are being sought. One of them is adding plant extracts to food to increase its antioxidant, anti-inflammatory and anti-cancerogenic activity. The aim of the study was to examine the effect of different wild-grown fruits (chokeberry, elderberry, hawthorn and sea-buckthorn) added to wheat-flour cookies on the proliferation of: (i) normal BJ lines (fibroblasts); (ii) tumor cells of the MCF-7 (breast cancer) and (iii) WM793 (melanoma) lines. Methanol-acetone extracts were prepared from previously baked wheat-flour cookies fortified with fruits in order to use them in the further part of the research to prepare mixtures with concentrations of 0.5 mg/mL; 1 mg/mL; 1.5 mg/mL; 2.5 mg/mL. The viability and cytotoxicity of normal and neoplastic cells was examined. It was observed that the WM793 melanoma tumor line appeared to be more susceptible to the action of the tested extracts with the addition of selected wild-grown fruits compared to MCF7 breast cancer cells. Moreover, the greatest significant effect on the inhibition of WM793 cells among extracts with a concentration of 2.5 mg/mL was proved in the case of sea-buckthorn (p < 0.05). In terms of the inhibition of the MCF7 line, the effect was proved only in the case of sea buckthorn (p < 0.05), while the viability of these neoplastic cells was at most affected by elderberry and chokeberry extracts (p < 0.05). [ABSTRACT FROM AUTHOR]

Ascorbate plays a vital role as a co-factor for a superfamily of enzymes, the 2-oxoglutarate dependent dioxygenases (2-OGDDs), which govern numerous pathways in cancer progression, including the hypoxic response and the epigenetic regulation of gene transcription. Ascorbate uptake into most cells is through active transport by the sodium-dependent vitamin C transporter 2 (SVCT2). The aims of this study were to determine the kinetics of ascorbate uptake and retention by breast cancer cell lines under various oxygen conditions, and to investigate the role of SVCT2 in mediating ascorbate uptake and intracellular trafficking. Human MDA-MB231 cells accumulated up to 5.1 nmol ascorbate/106 cells, human MCF7 cells 4.5 nmol/106 cells, and murine EO771 cells 26.7 nmol/106 cells. Intracellular ascorbate concentrations decreased rapidly after reaching maximum levels unless further ascorbate was supplied to the medium, and there was no difference in the rate of ascorbate loss under normoxia or hypoxia. SVCT2 was localised mainly to subcellular compartments, with the nucleus apparently containing the most SVCT2 protein, followed by the mitochondria. Much less SVCT2 staining was observed on the plasma membrane. Our data showed that careful management of the doses and incubation times with ascorbate in vitro allows for an approximation of in vivo conditions. The localisation of SVCT2 suggests that the distribution of ascorbate to intracellular compartments is closely aligned to the known function of ascorbate in supporting 2-OGDD enzymatic functions in the organelles and with supporting antioxidant protection in the mitochondria. [ABSTRACT FROM AUTHOR]

Abstract Background Microelectrical Impedance Spectroscopy (µEIS) is a tiny device that utilizes fluid as a working medium in combination with biological cells to extract various electrical parameters. Dielectric parameters of biological cells are essential parameters that can be extracted using µEIS. µEIS has many advantages, such as portability, disposable sensors, and high-precision results. Results The paper compares different configurations of interdigitated microelectrodes with and without a passivation layer on the cell contact tracks. The influence of the number of electrodes on the enhancement of the extracted impedance for different types of cells was provided and discussed. Different types of cells are experimentally tested, such as viable and non-viable MCF7, along with different buffer solutions. This study confirms the importance of µEIS for in vivo and in vitro applications. An essential application of µEIS is to differentiate between the cells’ sizes based on the measured capacitance, which is indirectly related to the cells’ size. The extracted statistical values reveal the capability and sensitivity of the system to distinguish between two clusters of cells based on viability and size. Conclusion A completely portable and easy-to-use system, including different sensor configurations, was designed, fabricated, and experimentally tested. The system was used to extract the dielectric parameters of the Microbeads and MCF7 cells immersed in different buffer solutions. The high sensitivity of the readout circuit, which enables it to extract the difference between the viable and non-viable cells, was provided and discussed. The proposed system can extract and differentiate between different types of cells based on cells’ sizes; two other polystyrene microbeads with different sizes are tested. Contamination that may happen was avoided using a Microfluidic chamber. The study shows a good match between the experiment and simulation results. The study also shows the optimum number of interdigitated electrodes that can be used to extract the variation in the dielectric parameters of the cells without leakage current or parasitic capacitance.

The identification of new genes/proteins involved in breast cancer (BC) occurrence is widely used to discover novel biomarkers and understand the molecular mechanisms of BC initiation and progression. The jumping translocation breakpoint (JTB) gene may act both as a tumor suppressor or oncogene in various types of tumors, including BC. Thus, the JTB protein could have the potential to be used as a biomarker in BC, but its neoplastic mechanisms still remain unknown or controversial. We previously analyzed the interacting partners of JTBhigh protein extracted from transfected MCF7 BC cell line using SDS-PAGE complemented with in-solution digestion, respectively. The previous results suggested the JTB contributed to the development of a more aggressive phenotype and behavior for the MCF7 BC cell line through synergistic upregulation of epithelial–mesenchymal transition (EMT), mitotic spindle, and fatty acid metabolism-related pathways. In this work, we aim to complement the previously reported JTB proteomics-based experiments by investigating differentially expressed proteins (DEPs) and tumorigenic pathways associated with JTB overexpression using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Statistically different gel spots were picked for protein digestion, followed by nanoliquid chromatography–tandem mass spectrometry (nLC-MS/MS) analysis. We identified six DEPs related to the JTBhigh condition vs. control that emphasize a pro-tumorigenic (PT) role. Twenty-one proteins, which are known to be usually overexpressed in cancer cells, emphasize an anti-tumorigenic (AT) role when low expression occurs. According to our previous results, proteins that have a PT role are mainly involved in the activation of the EMT process. Interestingly, JTB overexpression has been correlated here with a plethora of significant upregulated and downregulated proteins that sustain JTB tumor suppressive functions. Our present and previous results sustain the necessity of the complementary use of different proteomics-based methods (SDS-PAGE, 2D-PAGE, and in-solution digestion) followed by tandem mass spectrometry to avoid their limitations, with each method leading to the delineation of specific clusters of DEPs that may be merged for a better understanding of molecular pathways and neoplastic mechanisms related to the JTB's role in BC initiation and progression. [ABSTRACT FROM AUTHOR]

Background and purpose: Primary and metastatic breast cancers still represent an unmet clinical need for improved chemotherapy and hormone therapy. Considerable attention has been paid to natural anticancer compounds, especially lignans. The study aimed to evaluate the activity of several lignans against breast cancer cells and assess the effect of leading lignans on signaling pathways in combination with metformin. Experimental approach: Human breast cancer cell lines MCF7 (hormone-dependent), MDA-MB-231, and SKBR3 (hormone-independent) were used. A hormone-resistant MCF7/hydroxytamoxifen (HT) subline was obtained by long-term cultivation of the MCF7 line with hydroxytamoxifen. Antiproliferative activity was assessed by the MTT test; the expression of signaling pathway proteins was evaluated by immunoblotting analysis. Findings/Results: We evaluated the antiproliferative activity of lignans in breast cancer cells with different levels of hormone dependence and determined the relevant IC50 values. Honokiol was chosen as the leading compound, and its IC50 ranged from 12 to 20 µM, whereas for other tested lignans, the IC50 exceeded 50 µM. The accumulation of cleaved PARP and a decrease in the expression of Bcl-2 and ERα in MCF7/HT were induced following the combination of honokiol with metformin. Conclusions and implications: Honokiol demonstrated significant antiproliferative activity against both hormone-dependent breast cancer cells and lines with primary and acquired hormone resistance. The combination of honokiol with metformin is considered an effective approach to induce death in hormoneresistant cells. Honokiol is of interest as a natural compound with antiproliferative activity against breast cancers, including resistant tumors. [ABSTRACT FROM AUTHOR]

Purpose: Eliminating cancer stem cells (CSCs) is a challenge because of their enhanced resistance to anti-cancer drugs. Vitamin C, which is insufficient in patients with higher stages of cancer, has been gaining attention as a potential treatment for human malignancies. Hence this study aimed to analyze the effect of high-dose vitamin C treatment on the gene expression level of HIF- 1α, NF-αB1, BAX, and DNMT1 in the MCF7 cells undergoing hypoxia, as an inducer of CSCs characteristics. As a result, vitamin C could be possibly used as a promising therapeutic adjuvant. Methods: Here we first analyzed the breast CSC population alteration in MCF7 cells following hypoxia induction. Then, we evaluated the impact of vitamin C treatment on the gene expression level of four stemness-related genes in hypoxic MCF7 cells. Results: Our results indicate that vitamin C could reduce proliferation and stemness states in CSCs possibly by induction of apoptotic markers such as BAX, along with attenuating stemness markers, including NF-κB1, and DNMT1 gene expressions. Conclusion: According to our findings, vitamin C administration would become a new approach to avoiding the stimulation of CSCs during cancer therapies. [ABSTRACT FROM AUTHOR]

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Cotinus coggygria Scop. is a valuable medicinal plant species with pronounced pharmacological potential due to its numerous biological activities. The herb is characterized by a high content of polyphenols among which is fustin. The anticancer activities of fustin, however, are extremely weakly studied. The aim of the present study was to investigate the in vitro antiproliferative potential of fustin isolated from the heartwood of C. coggygria against cell lines originating from two of the most common cancer types – breast (MDA-MB-231 and MCF7), and colon cancer (Colon 26).

Introduction: Breast cancer can be caused by a mutation in its genome. Some mutations are cancerpredisposition which exist at the moment of germ cell genesis. It has been discovered that BRCA1 and BRCA2 are linked to hereditary breast cancer. BRCA1/2 are tumor suppressor genes involved in DNA repair and transcriptional regulation in response to DNA damage. Irradiation, particularly ionizing radiation used in clinical radiotherapy, causes DNA damage. This study aims to find out whether different doses of x-radiation might change the expression of BRCA1/2. Material and Methods: Cancer and normal breast cell lines (MCF10-A and MCF7) cultured in flasks were irradiated with X-rays in different doses including 50, 100, 400, 2000, and 4000 mGy. Then, the expression of BRCA1/2 genes was measured using real-time quantitative reverse transcription PCR (RT-qPCR). Relative changes for mRNA were calculated based on the ΔΔCt method. Results: MCF-10A cells represent a significant increase in BRCA2 expression at all irradiation doses while increasing the mRNA level for the BRCA1 gene observed after exposure to 50, 100, and 2000 mGy. This figure shows overexpression of BRCA2 gene after all irradiation doses except 100 mGy for MCF7 cells. The BRCA1 gene upregulated after exposure to 400 and 2000 mGy and downregulated at 50,100 and 4000 mGy in these cells. Conclusion: Incidence of cancer initiation was probable in normal breast cells after low-dose radiation, with up-regulation of BRCA1 and BRCA2 gene expression. BRCA mutation may be an inadequate outcome predictor of survival rate and other factors may be involved too. [ABSTRACT FROM AUTHOR]

Purpose: To determine the effect of melatonin in combination with capecitabine on the proliferation and induction of apoptosis in MCF-7 and SK-BR-3 breast cancer cell lines. Methods: The MTT assay (3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide) was performed to investigate the effect of capecitabine and in combination with melatonin on cell lines and to determine the half-maximal concentration (IC50) and combination index. Expression of apoptotic markers, Bax, Bcl-2, and caspase-3 were measured by polymerase chain reaction (PCR) after treatment. Results: The IC50 of melatonin and capecitabine in MCF-7 and SK-BR-3 cell lines were 4.52 mM and 619.36 µg/mL, and 5.1 mM and 679.51 µg/mL, respectively. The combined use of melatonin and capecitabine significantly reduced IC50. Also, combination index (CI) values were < 1, indicating that the combination of capecitabine and melatonin has a synergistic effect. The results of gene expression also showed enhancement in the Bax/Bcl-2 ratio in melatonin-capecitabine combination compared with capecitabine alone in both cell lines. Conclusion: Melatonin-capecitabine-induced cell death is controlled by caspase-3 and Bax/Bcl-2- dependent apoptosis. The combination of melatonin and capecitabine has a synergistic effect on both HER2+ and HER2- cells. [ABSTRACT FROM AUTHOR]

In this study, four types of basil seed extracts were used, being cold aqueous extract, hot aqueous extract, petroleum ether extract, and methanolic extract.Nine concentrations (10000, 5000, 2500, 1250, 625, 312.56, 156.25, 78.125, 39.0, 0.0) µg/ml were used to study the extracts cytotoxicity against two breast cancer cell lines MCF7 and AMJ13 beside REF cell line as normal cells. The methanol extract showed the highest inhibition rate of 64.4% on MCF7 cell line at concentration of 1250 µg/ml and 42.4% on AMJ13 cell line at a concentration of 39.0 µg/ml with significant difference as compared to control sample during the 72hr exposure period. While the petroleum ether extract showed a lower inhibition rate of 16.02% at a concentration of 78.1 µg/ml on MCF7 cell line and 35.3 % at a concentration of 312.5 µg /ml on AMJ13 cells during a 72hr exposure period, compared with the two aqueous extracts which showed a slight effect compared to the control. The cold aqueous extract showed the slight effect of 24.4% at a concentration of 5000 µg/ml on AMJ13 cell line and no toxicity was shown on MCF7 cells. All extracts showed no effect on REF normal cells. In all effective concentrations the basil seed extracts caused a damage to the DNA that cannot be repaired, and thus the cells are heading to programmed death. This effect on the genetic material was studied using the comet assay and mitotic index. [ABSTRACT FROM AUTHOR]

Human breast adenocarcinoma is a form of cancer which has the tendency to metastasize to other tissues, including bones, lungs, brain, and liver. Several chemotherapeutic drugs are used to treat breast tumors. Their combination is used to simultaneously target different mechanisms involved in cell replication. Radio electric asymmetric conveyer (REAC) technology is an innovative technology, used both in vitro and in vivo, to induce cell reprogramming and counteract senescence processes. Within this context, we treated MCF-7 cells with a regenerative (RGN) REAC treatment for a period ranging between 3 and 7 days. We then analyzed cell viability by trypan blue assays and gene and protein expression by real time-qPCR and confocal microscope, respectively. We also detected the levels of the main proteins involved in tumor progression, DKK1 and SFRP1, by ELISA and cell senescence by β-galactosidase tests. Our results showed the ability of REAC RGN to counteract MCF-7 proliferation, probably inducing autophagy via the upregulation of Beclin-1 and LC3-I, and the modulation of specific tumorigenic biomarkers, such as DKK1 and SPFR1. Our results could suggest the application of the REAC RGN in future in vivo experiments, as an aid for the therapeutic strategies usually applied for breast cancer treatment. [ABSTRACT FROM AUTHOR]

The present study investigates the bioactive properties of the Ethyl Acetate Extract of Inonotus obliquus (EAEIO), sourced from the Chaga mushroom. Traditionally used in medicine, this mushroom is increasingly recognized for its potent antimicrobial and anticancer benefits. Our analysis sought to explore the impact of EAEIO on four diverse bacterial strains: Escherichia coli ATCC25922, Bacillus cereus EMCC1080, Pseudomonas aeruginosa ATCC10145, and Listeria monocytogenes NCTC7973, employing the disc diffusion method. We also investigated the potential cytotoxic effect of EAEIO on MCF7 breast cancer cells, HCT16 colon cells, and normal BHK cells using the MTT assay. Our results underscore the effective antimicrobial properties of EAEIO, evidenced by inhibition zones between 16 mm to 28 mm and minimum inhibitory concentrations (MICs) ranging from 6.25 µg/mL to 1.563 µg/mL. In addition, the EAEIO demonstrated remarkable anticancer activity against MCF7 and HCT16 cell lines, with IC50 values of 7.56 µg/mL and 11.2 µg/mL, respectively. To conclude, EAEIO - the Ethyl Acetate Extract of the Chaga mushroom, exhibited significant antimicrobial and anticancer properties while showing no toxic effect on BHK cells. These observations suggest EAEIO's potential as a valuable natural resource for antimicrobial and anticancer treatments. However, further research is essential to verify the safety and efficacy of EAEIO in cancer and infectious disease management. [ABSTRACT FROM AUTHOR]