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Despite rapid advancement in research of diagnostics and therapeutics, cancer is the most dangerous disease‐causing millions of deaths worldwide. Many of the conventional anticancer therapies can even lead to developing resistance to therapy and recurrence of cancer. To find a new, alternative treatment strategy for a variety of ailments scientists and researchers have turned their attention to cell therapies and regenerative medicine. Stem cells are now being researched for their extensive potential application in therapy for several incurable illnesses including cancer. One of the most often employed cell types for regenerative medicine is mesenchymal stem cells. Mesenchymal stem cells (MSCs) are considered a promising source of stem cells in personalized cell‐based therapies. The inherent tumor tropic and immune‐modulatory properties of MSCs can be used to target cancer cells. This review aims to focus on the anticancer properties of MSCs and their effect on different signaling pathways. Later on, we discuss the advantages of engineered MSCs over non‐engineered MSCsin cancer therapy. [ABSTRACT FROM AUTHOR]

Silver polyacrylate (argacryl) is shown to have antitumor activity in models of solid mouse tumors in vivo and a cytotoxic effect on human tumor cells in vitro. Argacryl enhances the antitumor effect of cisplatin (Lewis lung carcinoma in mice) and does not show cross resistance with cisplatin and doxorubicin (human breast cancer MCF-7). The molecular mechanism of action of argacryl could be associated with the induction of single-strand DNA breaks in the absence of crosslinking in the DNA molecule. [ABSTRACT FROM AUTHOR]

Copyright of Chemistry & Industry of Forest Products is the property of Chemistry & Industry of Forest Products Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Shenyang Pharmaceutical University is the property of Shenyang Pharmaceutical University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Marine fungi, such as species from the Penicillium and Aspergillus genera, are prolific producers of a diversity of natural products with cytotoxic properties. These fungi have been successfully isolated and identified from various marine sources, including sponges, coral, algae, mangroves, sediment, and seawater. The cytotoxic compounds derived from marine fungi can be categorized into five distinct classes: polyketides, peptides, terpenoids and sterols, hybrids, and other miscellaneous compounds. Notably, the pre-eminent group among these compounds comprises polyketides, accounting for 307 out of 642 identified compounds. Particularly, within this collection, 23 out of the 642 compounds exhibit remarkable cytotoxic potency, with IC50 values measured at the nanomolar (nM) or nanogram per milliliter (ng/mL) levels. This review elucidates the originating fungal strains, the sources of isolation, chemical structures, and the noteworthy antitumor activity of the 642 novel natural products isolated from marine fungi. The scope of this review encompasses the period from 1991 to 2023. [ABSTRACT FROM AUTHOR]

Based on the results of our own preliminary studies, the derivative of the marine alkaloid fascaplysin containing a phenyl substituent at C-9 was selected to evaluate the therapeutic potential in vivo and in vitro. It was shown that this compound has outstandingly high antimicrobial activity against Gram-positive bacteria, including antibiotic-resistant strains in vitro. The presence of a substituent at C-9 of the framework is of fundamental importance, since its replacement to neighboring positions leads to a sharp decrease in the selectivity of the antibacterial action, which indicates the presence of a specific therapeutic target in bacterial cells. On a model of the acute bacterial sepsis in mice, it was shown that the lead compound was more effective than the reference antibiotic vancomycin seven out of nine times. However, ED50 value for 9-phenylfascaplysin (7) was similar for the unsubstituted fascaplysin (1) in vivo, despite the former being significantly more active than the latter in vitro. Similarly, assessments of the anticancer activity of compound 7 against various variants of Ehrlich carcinoma in mice demonstrated its substantial efficacy. To conduct a structure–activity relationship (SAR) analysis and searches of new candidate compounds, we synthesized a series of analogs of 9-phenylfascaplysin with varying aryl substituents. However, these modifications led to the reduced aqueous solubility of fascaplysin derivatives or caused a loss of their antibacterial activity. As a result, further research is required to explore new avenues for enhancing its pharmacokinetic characteristics, the modification of the heterocyclic framework, and optimizing of treatment regimens to harness the remarkable antimicrobial potential of fascaplysin for practical usage. [ABSTRACT FROM AUTHOR]

The 1,8-Diazaanthracene-2,9,10-triones, their 5,8-dihydro derivatives, and 1,8-diazaanthracene-2,7,9,10-tetraones, structurally related to the diazaquinomycin family of natural products, were synthesized in a regioselective fashion employing Diels–Alder strategies. These libraries were studied for their cytotoxicity in a variety of human cancer cell lines in order to establish structure–activity relationships. From the results obtained, we conclude that some representatives of the 1,8-diazaanthracene-2,9,10-trione framework show potent and selective cytotoxicity against solid tumors. Similar findings were made for the related 1-azaanthracene-2,9,10-trione derivatives, structurally similar to the marcanine natural products, which showed improved activity over their natural counterparts. An enantioselective protocol based on the use of a SAMP-related chiral auxiliary derived was developed for the case of chiral 5-substituted 1,8-diazaanthracene-2,9,10-triones, and showed that their cytotoxicity was not enantiospecific. [ABSTRACT FROM AUTHOR]

Five artemisinin bivalent ligands molecules 4a–4e were designed, synthesized, and confirmed by 1H NMR, 13C NMR, and low-resolution mass spectrometry, and the bioactivities of the target compounds were investigated against four human tumor cell lines in vitro, including BGC-823, HepG-2, MCF-7, and HCT-116. The results showed 4a, 4d, and 4e exhibited significantly tumor cell inhibitory activity compared with the artemisinin and dihydroartemisinin; compound 4e has good biological activity inhibiting BGC-823 with an IC50 value of 8.30 μmol/L. Then, the good correlations with biological results were validated by molecular docking through the established bivalent ligands multi-target model, which showed that 4e could bind well with the antitumor protein MMP-9. [ABSTRACT FROM AUTHOR]

A new class of palladium–indenyl complexes characterized by the presence of one bulky alkyl isocyanide and one aryl phosphine serving as ancillary ligands has been prepared, presenting high yields and selectivity. All the new products were completely characterized using spectroscopic and spectrometric techniques (NMR, FT-IR, and HRMS), and, for most of them, it was also possible to define their solid-state structures via X-ray diffractometry, revealing that the indenyl fragment always binds to the metal centre with a hapticity intermediate between ƞ3 and ƞ5. A reactivity study carried out using piperidine as a nucleophilic agent proved that the indenyl moiety is the eligible site of attack rather than the isocyanide ligand or the metal centre. All complexes were tested as potential anticancer agents against three ovarian cancer cell lines (A2780, A2780cis, and OVCAR-5) and one breast cancer cell line (MDA-MB-231), displaying comparable activity with respect to cisplatin, which was used as a positive control. Moreover, the similar cytotoxicity observed towards A2780 and A2780cis cells (cisplatin-sensitive and cisplatin-resistant, respectively) suggests that our palladium derivatives presumably act with a mechanism of action different than that of the clinically approved platinum drugs. For comparison, we also synthesized Pd-ƞ3-allyl derivatives, which generally showed a slightly higher activity towards ovarian cancer cells and lower activity towards breast cancer cells with respect to their Pd-indenyl congeners. [ABSTRACT FROM AUTHOR]

In this study, we described physico-chemical properties of novel nanoformulation of photosensitizer-pyropheophorbide α 17-diethylene glycol ester (XL) (chlorophyll α derivative), revealing insights into antitumor activity and maintaining quality, meeting the pharmaceutical approach of new nanoformulation design. Our formulation, based on poly(lactic-co-glycolic acid) (PLGA) nanoparticles, increased XL solubility and selective tumor-targeted accumulation. In our research, we revealed, for the first time, that XL binding to polyvinyl alcohol (PVA) enhances XL photophysical activity, providing the rationale for PVA application as a stabilizer for nanoformulations. Results of FTIR, DSC, and XRD revealed the physical interactions between XL and excipients, including PVA, indicating that the encapsulation maintained XL binding to PVA. The encapsulated XL exhibited higher photophysical activity compared to non-encapsulated substance, which can be attributed to the influence of residual PVA. Gamma-irradiation led to degradation of XL; however, successful sterilization of the samples was achieved through the filtration. Importantly, the encapsulated and sterilized XL retained cytotoxicity against both 2D and 3D tumor cell models, demonstrating the potential of the formulated NP–XL for photodynamic therapy applications, but lacked the ability to reactivate epigenetically silenced genes. These findings provide valuable insights into the design and characterization of PLGA-based nanoparticles for the encapsulation of photosensitizers. [ABSTRACT FROM AUTHOR]

Quercetin is a flavonoid with significant biological and pharmacological activity. In this paper, quercetin was modified at the 3-OH position. Rutin was used as a raw material. We used methyl protection, Williamson etherification reactions, and then substitution reactions to prepare 15 novel quercetin derivatives containing a quinoline moiety. All these complexes were characterized by 1H NMR, 13C NMR, IR and HRMS. Of these, compound 3e (IC50 = 6.722 μmol·L−1) had a better inhibitory effect on human liver cancer (HepG-2) than DDP (Cisplatin) (IC50 = 26.981 μmol·L−1). The mechanism of the action experiment showed that compound 3e could induce cell apoptosis. [ABSTRACT FROM AUTHOR]

This study reports the synthesis and structural characterization of a series of novel acetamide-derived compounds containing a methylsulfonyl unit. The in vitro antibacterial activity results demonstrated that compound 2-((4-fluorophenyl)sulfonyl)-N-(4-(methylsulfonyl)phenyl)acetamide (6b) exhibited superior antibacterial activities against Xanthomonas oryzae pv. oryzicolaby (Xoc), Xanthomonas oryzae pv. oryzae (Xoo), and Xanthomonas axonopodis pv. citri (Xac) at 100 μg/mL concentration, with the inhibition rates of 86.24%, 81.59%, and 75.65%, respectively, compared to Bismerthiazol and Thiodiazole copper. Meanwhile, the in vitro antifungal activities of all target compounds were found to be lower against Mucor fragilis (M. fragilis), Mucor bainieri (M. bainieri), and Trichoderma atroviride (T. atroviride) at 50 μg/mL concentration, with the inhibition rates of 0–45.21%, 0–30.24%, and 0–12.65%, respectively, compared to Carbendazim. Moreover, bioassay results of the target compounds against prostate cancer (PC3), hepatocellular carcinoma (HepG2), and leukemia (K562) cells at 10 μM concentration demonstrated that, compared to 5-fluorouracil, compound 2-((4-fluorophenyl)thio)-N-(4-(methylsulfonyl)phenyl)acetamide (4c) illustrated obvious antitumor activity (56.87%) against K562. This work first highlights the effect of the modification of the acetamide-derived compounds bearing a methylsulfonyl unit on the bioactivity evaluation. [ABSTRACT FROM AUTHOR]

Acetylcholinesterase (AchE) is a serine hydrolase with classical function to degrade acetylcholine and terminate neurotransmission. While "nonclassical" functions of AchE were involved in cell growth, death, invasion, etc. The expression and activity of AchE is changed in tumors, suggesting AChE inhibitors (AchEIs) may serve as potential antitumor drugs. In this study, the antitumor activity of a series of 2‐phenylthiazole derivatives originally designed and synthesized as AchEIs were investigated. One compound named A6, was screened out with superior antitumor efficacy, especially against breast cancer MCF‐7 cells. A6 significantly disrupted the amino acid metabolism and inhibited migration of MCF‐7. In addition, A6 induced apoptosis of MCF‐7 cells. To clarify how A6 affected on MCF‐7 cells, RNA‐seq analysis was conducted to evaluate the whole genome effect of A6 on gene expression. A total of 153 genes were increased, and the expression of 81 genes was decreased. GO and KEGG enrichment analysis showed A6 treatment mainly disrupted sterol/cholesterol pathway, Ras signaling pathway, VEGF signaling pathway, etc. Moreover, bioinformatic analysis and cell viability test showed A6 plays anticancer role by regulating Best1 and HIST1H2BJ. These results indicate that AchEI A6 could be a potential antitumor agent for breast cancer patients and could help the development of novel therapies. [ABSTRACT FROM AUTHOR]

Eight new stigmasterol derivatives possessing 1,2,3-triazoles moiety were synthesized by a 1,3-dipolar cycloaddition reaction. All the compounds were characterized by IR, NMR, and HR-MS. In addition, human cervical cancer cells (HeLa), human gastric cancer cells (HGC-27), and human renal epithelial cells (HEK-293T) were selected to study the antitumor activity of the synthesized compounds. The results demonstrated that compounds 3c and 3d exhibited better inhibitory activity against the tested tumor cell lines. The IC50 value of the inhibitory activity on HeLa was 52.3 μmol·L–1 and 31.4 μmol·L–1, and 40.6 μmol·L–1 and 44.6 μmol·L–1 for HGC-27, respectively. [ABSTRACT FROM AUTHOR]

Background: Axitinib, a potent and selective inhibitor of vascular endothelial growth factor (VEGF) receptor (VEGFR) tyrosine kinase 1,2 and 3, is used in chemotherapy because it inhibits tumor angiogenesis by blocking the VEGF/VEGFR pathway. In veterinary medicine, attempts have been made to apply tyrosine kinase inhibitors with anti-angiogenic effects to tumor patients, but there are no studies on axitinib in canine mammary gland tumors (MGTs). Objectives: This study aimed to confirm the antitumor activity of axitinib in canine mammary gland cell lines. Methods: We treated canine MGT cell lines (CIPp and CIPm) with axitinib and conducted CCK, wound healing, apoptosis, and cell cycle assays. Additionally, we evaluated the expression levels of angiogenesis-associated factors, including VEGFs, PDGF-A, FGF-2, and TGF-β1, using quantitative real-time polymerase chain reaction. Furthermore, we collected canine peripheral blood mononuclear cells (PBMCs), activated them with concanavalin A (ConA) and lipopolysaccharide (LPS), and then treated them with axitinib to investigate changes in viability. Results: When axitinib was administered to CIPp and CIPm, cell viability significantly decreased at 24, 48, and 72 h ( p < 0.001), and migration was markedly reduced (6 h, p < 0.05; 12 h, p < 0.005). The apoptosis rate significantly increased ( p < 0.01), and the G2/M phase ratio showed a significant increase ( p < 0.001). Additionally, there was no significant change in the viability of canine PBMCs treated with LPS and ConA. Conclusion: In this study, we confirmed the antitumor activity of axitinib against canine MGT cell lines. Accordingly, we suggest that axitinib can be applied as a new treatment for patients with canine MGTs. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Chinese Institute of Food Science & Technology is the property of Journal of Chinese Institute of Food Science & Technology Periodical Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Elemene, derived from Curcuma wenyujin, one of the "8 famous genuine medicinal materials of Zhejiang province," exhibits remarkable antitumor activity. It has gained wide recognition in clinical practice for effectiveness on tumors. Dr. XIE Tian, introduced the innovative concept of "molecular compatibility theory" by combining Chinese medicine principles, specifically the "monarch, minister, assistant, and envoy" theory, with modern biomedical technology. This groundbreaking approach, along with a systematic analysis of Chinese medicine and modern biomedical knowledge, led to the development of elemene nanoliposome formulations. These novel formulations offer numerous advantages, including low toxicity, well-defined composition, synergistic effects on multiple targets, and excellent biocompatibility. Following the principles of the "molecular compatibility theory", further exploration of cancer treatment strategies and methods based on elemene was undertaken. This comprehensive review consolidates the current understanding of elemene's potential antitumor mechanisms, recent clinical investigations, advancements in drug delivery systems, and structural modifications. The ultimate goal of this review is to establish a solid theoretical foundation for researchers, empowering them to develop more effective antitumor drugs based on the principles of "molecular compatibility theory". [ABSTRACT FROM AUTHOR]

The aim. This review aims to provide a comprehensive understanding of dichloroacetic acid derivatives. We aim to cover all aspects of these compounds, including their chemical properties, various synthesis methods, and their wide range of applications in medicinal chemistry. By exploring their diverse roles in drug development, we aim to highlight their importance and potential in shaping future pharmaceutical innovation. Materials and methods. Bibliosemantic and analytical methods are used in the research. Results. Our studies confirm the potential effectiveness of dichloroacetic acid and its derivatives in the treatment of cancer and other diseases. These compounds can induce the apoptosis process, which is the programmed cell death, and inhibit the cancer cells' growth. This is particularly effective when dichloroacetic acid and its derivatives are used in combination with other therapeutic methods, as indicated in the patents cited in our study. Dichloroacetic acid and its derivatives have also shown the ability to lower blood glucose and cholesterol levels. This indicates the possibility of their use for diabetes, hyperlipidemia, and lactic acidosis treatment. Diabetes, hyperlipidemia, and lactic acidosis are serious conditions that can lead to significant health problems. Therefore, the possibility of using dichloroacetic acid and its derivatives for the treatment of these conditions opens new perspectives in medical science. Conclusions. Our findings point to the prospects of further research in the field of new therapy methods development and the use of dichloroacetic acid derivatives as potential drugs to improve the effectiveness of cancer and other diseases treatment. We believe that these compounds have great potential for further study and may play an important role in future medical innovation. [ABSTRACT FROM AUTHOR]

Background: The ethnic drug Melastoma dodecandrum Lour. (MDL) is an important medicinal plant with potential antitumor properties, which have been proposed as promising anticancer agents, but the material basis for its therapeutic effect is still unclear and lacks in-depth research. Methods: In this study, the in vitro antitumor effects of different MDL extracts in different gynecological tumor cells were investigated by CCK-8 assay. The active components of 21 batches of MDL samples collected from different product areas and markets were determined and compared by the UPLC method. On this basis, the data was processed with the fingerprint similarity software, and the correlation between MDL fingerprint and antihuman cervical cancer activity was further analyzed by a multivariate statistical method. Results: Five kinds of MDL extracts, including the aqueous extract, the crude polysaccharide, the total polyphenol, the ethyl acetate fraction of the aqueous extract and 50% ethanol extract, had inhibitory effects on human cervical cancer HeLa and SiHa cells, among which total polyphenols of MDL showed stronger inhibition effect on human cervical cancer cells. In addition, the fingerprint of the total polyphenols of MDL had sixteen common peaks, and six common peaks were checked by using diode array and UV spectra, among which peak 1 (gallic acid), peak 4 (protocatechuic acid), peak 12 (unknown), and peak 15 (ellagic acid) were negatively correlated with the IC50 value of the SiHa cells, and all variable importance values were greater than 1. Conclusion: Our data demonstrated that the main active components ofMDL inhibiting human cervical cancer SiHa cells may be the synergistic effect of gallic acid, protocatechuic acid and ellagic acid, and the further spectrum-effect relationship analysis provides an important reference and basis for the quality control and the development of new anticervical cancer drug of MDL. [ABSTRACT FROM AUTHOR]

Ligustrum ovalifolium (family Oleaceae) is a flowering plant with reported anti-inflammatory, antioxidant, hypotensive, and hypoglycemic activities. The present study investigated the phytochemical components and biological activities of L. ovalifolium leaves. Results showed that ethyl acetate extract has the highest potential to reduce cell growth in HeLa, T47D, and MDA-MB-231 cell lines with IC50 values of 0.047, 0.07, and 0.072 mg/mL, respectively. Based on the LD50 value, the tumor-bearing mice were IP injected with 12.5 mg/kg of ethyl acetate extract. Tumor growth was significantly reduced (-43.1%) compared to the control group. According to the LC-MS analysis, Apigenin-7-O-glucoside was the flavonoid with the highest percentage value in L. ovalifolium leaves. DPPH assay exhibited antioxidant activity of ethanol and water extracts with the percentage of scavenging around 91% at a concentration of 200 µg/mL. As well, the assessment of liver and kidney functions of the experimented animals showed no toxicity effect compared to the control result. All things considered, the outcomes of this study revealed an antitumor potential of L. ovalifolium leaves extracts, hence this activity may arise from the presence of different potent flavonoids and the antioxidant potential. Nevertheless, further investigations are needed to determine the targets and signaling pathways that are affected by L. ovalifolium leaves extracts. [ABSTRACT FROM AUTHOR]

Breast cancer patients with high levels of human epidermal growth factor receptor 2 (HER2) expression have worse clinical outcomes. Anti‐HER2 monoclonal antibody (mAb) is the most important therapeutic modality for HER2‐positive breast cancer. We previously immunized mice with the ectodomain of HER2 to create the anti‐HER2 mAb, H2Mab‐77 (mouse IgG1, kappa). This was then altered to produce H2Mab‐77‐mG2a‐f, an afucosylated mouse IgG2a. In the present work, we examined the reactivity of H2Mab‐77‐mG2a‐f and antitumor effects against breast cancers in vitro and in vivo. BT‐474, an endogenously HER2‐expressing breast cancer cell line, was identified by H2Mab‐77‐mG2a‐f with a strong binding affinity (a dissociation constant [KD]: 5.0 × 10−9 M). H2Mab‐77‐mG2a‐f could stain HER2 of breast cancer tissues in immunohistochemistry and detect HER2 protein in Western blot analysis. Furthermore, H2Mab‐77‐mG2a‐f demonstrated strong antibody‐dependent cellular cytotoxicity (ADCC) and complement‐dependent cytotoxicity (CDC) for BT‐474 cells. MDA‐MB‐468, a HER2‐negative breast cancer cell line, was unaffected by H2Mab‐77‐mG2a‐f. Additionally, in the BT‐474‐bearing tumor xenograft model, H2Mab‐77‐mG2a‐f substantially suppressed tumor development when compared with the control mouse IgG2a mAb. In contrast, the HER2‐negative MDA‐MB‐468‐bearing tumor xenograft model showed no response to H2Mab‐77‐mG2a‐f. These findings point to the possibility of H2Mab‐77‐mG2a‐f as a treatment regimen by showing that it has antitumor effects on HER2‐positive breast tumors. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Shenyang Pharmaceutical University is the property of Shenyang Pharmaceutical University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The present study focused on the design and preparation of acid-responsive benzimidazole-chitosan quaternary ammonium salt (BIMIXHAC) nanogels for a controlled, slow-release of Doxorubicin HCl (DOX.HCl). The BIMIXHAC was crosslinked with sodium tripolyphosphate (TPP) using the ion crosslinking method. The method resulted in nanogels with low polydispersity index, small particle size, and positive zeta potential values, indicating the good stability of the nanogels. Compared to hydroxypropyl trimethyl ammonium chloride chitosan-Doxorubicin HCl-sodium tripolyphosphate (HACC-D-TPP) nanogel, the benzimidazole-chitosan quaternary ammonium salt-Doxorubicin HCl-sodium tripolyphosphate (BIMIXHAC-D-TPP) nanogel show higher drug encapsulation efficiency and loading capacity (BIMIXHAC-D-TPP 93.17 ± 0.27% and 31.17 ± 0.09%), with acid-responsive release profiles and accelerated release in vitro. The hydroxypropyl trimethyl ammonium chloride chitosan-sodium tripolyphosphate (HACC-TPP), and benzimidazole-chitosan quaternary ammonium salt-sodium tripolyphosphate (BIMIXHAC-TPP) nanogels demonstrated favorable antioxidant capability. The assay of cell viability, measured by the MTT assay, revealed that nanogels led to a significant reduction in the cell viability of two cancer cells: the human lung adenocarcinoma epithelial cell line (A549) and the human breast cancer cell line (MCF-7). Furthermore, the BIMIXHAC-D-TPP nanogel was 2.96 times less toxic than DOX.HCl to the mouse fibroblast cell line (L929). It was indicated that the BIMIXHAC-based nanogel with enhanced antioxidant and antitumor activities and acidic-responsive release could serve as a potential nanocarrier. [ABSTRACT FROM AUTHOR]

Dietary supplementation is proposed as a strategy to reduce the side effects of conventional chemotherapy for triple-negative breast cancer (TNBC). Chitosan oligosaccharides (COS), a functional carbohydrate, have been identified to potentially inhibit cancer cell proliferation. However, a detailed investigation is required to fully understand its exact influence, particularly in terms of COS composition. The antitumor activities of COS oligomers and its monomer of glucosamine, when combined with doxorubicin separately, were evaluated in MDA-MB-231 cells. Chitotriose was identified to have the most significant synergistic effect. Preincubation with chitotriose was observed to promote the entry of doxorubicin into the cell nuclei and induce morphological changes in the cells. Mechanism analysis at the transcriptional level revealed that the early growth response 1 (Egr1) gene was a key regulator in enhancing the suppressive effect. This gene was found to modulate the activity of its downstream gene, growth arrest, and DNA damage-inducible alpha (Gadd45a). The role of Egr1 was confirmed through a small interfering RNA test and function assay. These findings provide insight into the effect and underlying mechanism of chitotriose supplementation for TNBC therapy. [ABSTRACT FROM AUTHOR]

A series of new quinoline derivatives were designed, synthesized and evaluated for antiproliferative activity against two cancer cell lines (MCF-7 and HCCLM-3) and a human normal cell line (HEK293T cells). Among them, 3-(2,7-dimethoxyquinolin-3-yl)-1-(4-methoxyphenyl)prop-2-en-1-one displayed the most inhibitory activity against MCF-7 and HCCLM-3 cells, which were equal and better than the positive control 5-fluorouracil (82.18% vs. 83.29%, 94.79% vs. 76.98%), respectively. Additionally, it had poor inhibitory activity (48.14%) against HEK293T cells, which displayed good selectivity for cancer cells. Therefore, 3-(2,7-dimethoxyquinolin-3-yl)-1-(4-methoxyphenyl)prop-2-en-1-one could be as a lead compound to develop more potent anticancer agents. [ABSTRACT FROM AUTHOR]

In retrospective studies, metformin use has been associated with better clinical outcomes in diabetic patients with advanced, well-differentiated neuroendocrine tumors (WDNETs). However, prospective evidence of metformin safety and activity is lacking. Here, we conducted the first-in-human phase Ib MetNET2 trial to investigate the safety and antitumor activity of metformin in combination with the somatostatin analog lanreotide autogel (ATG) in both diabetic and non-diabetic patients with advanced WDNETs of the gastrointestinal (GI) or thoracic tract. Enrolled patients received lanreotide ATG 120 mg plus oral metformin, up to a maximum dosage of 2550 mg/day. We enrolled 20 patients, of whom 18 (90%) and 2 (10%) had WDNETs of the GI and thoracic tract, respectively. Fourteen patients (70%) were non-diabetic. With a 5% incidence of SAEs, the study met its primary objective of demonstrating treatment safety. With a median follow-up of 39 months (95% CI 28-NE), median PFS was 24 months (95% CI 16-NE), with 12-month and 24-month PFS probability of 75% (95% CI 58–97) and 49% (95% CI 31–77), respectively. We found no statistically significant PFS differences between diabetic and non-diabetic patients. Among exploratory analyses, the presence of tumor genomic alterations in DNA damage pathways was associated with trend towards worse PFS, whereas a precocious reduction of HOMA-IR index and plasma cholesterol concentration showed a trend towards an association with better PFS. In conclusion, metformin plus lanreotide ATG is a safe and well tolerated combination treatment that is associated with promising antitumor activity in both non-diabetic and diabetic patients with WDNETs, and that warrants further investigation in larger clinical trials. [ABSTRACT FROM AUTHOR]

Nur77 modulators have emerged as a promising therapeutic approach for hepatocellular carcinoma. In this study, a structure-based rational drug design approach was used to design and synthesise a series of 4-((8-hydroxy-2-methylquinolin-4-yl)amino)benzoylhydrazone derivatives based on the binding characteristics of our previously reported 10g and the native ligand 3NB at the binding Site C of Nur77. Cell-based cytotoxicity assays revealed that compound TMHA37 demonstrated the highest cytotoxicity against all tested cancer cells. The induced fit docking and binding pose metadynamics simulation suggested that TMHA37 was the most promising Nur77 binder at Site C. Molecular dynamics simulation validated the stable binding of TMHA37 to Nur77's Site C but not to Sites A or B. Specifically, TMHA37 bound strongly to Nur77-LBD (KD = 445.3 nM) and could activate Nur77's transcriptional activity. Furthermore, TMHA37 exhibited antitumor effects by blocking the cell cycle at G2/M phase and inducing cell apoptosis in a Nur77-dependent manner. [ABSTRACT FROM AUTHOR]

In the present study, 5-arylidene rhodanine derivatives 3a–f, N-glucosylation rhodanine 6, S-glucosylation rhodanine 7, N-glucoside rhodanine 8 and S-glucosylation 5-arylidene rhodanines 13a–c were synthesised and screened for cytotoxicity against a panel of cancer cells with investigating the effective molecular target and mechanistic cell death. The anomers were separated by flash column chromatography and their configurations were assigned by NMR spectroscopy. The stable structures of the compounds under study were modelled on a molecular level, and DFT calculations were carried out at the B3LYP/6-31 + G (d,p) level to examine their electronic and geometric features. A good correlation between the quantum chemical descriptors and experimental observations was found. Interestingly, compound 6 induced potent cytotoxicity against MCF-7, HepG2 and A549 cells, with IC50 values of 11.7, 0.21, and 1.7 µM, compared to Dox 7.67, 8.28, and 6.62 µM, respectively. For the molecular target, compound 6 exhibited topoisomerase II inhibition and DNA intercalation with IC50 values of 6.9 and 19.6 µM, respectively compared to Dox (IC50 = 9.65 and 31.27 µM). Additionally, compound 6 treatmnet significantly activated apoptotic cell death in HepG2 cells by 80.7-fold, it induced total apoptosis by 34.73% (23.07% for early apoptosis, 11.66% for late apoptosis) compared to the untreated control group (0.43%) arresting the cell population at the S-phase by 49.6% compared to control 39.15%. Finally, compound 6 upregulated the apoptosis-related genes, while it inhibted the Bcl-2 expression. Hence, glucosylated rhodanines may serve as a promising drug candidates against cancer with promising topoisomerase II and DNA intercalation. [ABSTRACT FROM AUTHOR]

A series of 1H-benzo[f]chromene moieties (4a–z) were synthesised under Ultrasonic irradiation and confirmed with spectral analyses. Derivative 4i solely possessed an X-ray single crystal. The anti-proliferative efficacy of the desired molecules has been explored against three cancer cells: MCF-7, HCT-116, and HepG-2 with the cytotoxically active derivatives screened against MCF-7/ADR and normal cells HFL-1 and WI-38. Furthermore, compounds 4b–d, 4k, 4n, 4q, and 4w, which possessed good potency against MCF-7/ADR, were tested as permeability glycoprotein (P-glycoprotein [P-gp]) expression inhibitors. The attained data confirmed that 4b–d, 4q, and 4w exhibited strong expression inhibition against the P-gp alongside its cytotoxic effect on MCF-7/ADR. The western blot results and Rho123 accumulation assays showed that compounds 4b–d, 4q, and 4w effectively inhibited the P-gp expression and efflux function. Meanwhile, 4b–d, 4q, and 4w induced apoptosis and accumulation of the treated MCF-7/ADR cells in the G1 phase and 4k and 4n in the S phase of the cell cycle. [ABSTRACT FROM AUTHOR]

Inhibition of PI3K pathway has become a desirable strategy for cancer treatment. In this work, a series of 2, 6, 8-substituted Imidazo[1,2-a]pyridine derivatives were designed and screened for their activities against PI3Kα and a panel of PI3Kα-addicted cancer cells. Among them, compound 35 was identified as a PI3Kα inhibitor with nanomolar potency as well as acceptable antiproliferative activity. Flow cytometry analysis confirmed 35 induced cell cycle arrest and apoptosis in T47D cells. In addition, it also showed desirable in vitro ADME properties. The design, synthesis, and SAR exploration of 35 are described within. [ABSTRACT FROM AUTHOR]

The coating of liposomes with polyethyleneglycol (PEG) has been extensively discussed over the years as a strategy for enhancing the in vivo and in vitro stability of nanostructures, including doxorubicin-loaded liposomes. However, studies have shown some important disadvantages of the PEG molecule as a long-circulation agent, including the immunogenic role of PEG, which limits its clinical use in repeated doses. In this context, hydrophilic molecules as carbohydrates have been proposed as an alternative to coating liposomes. Thus, this work studied the cytotoxicity and preclinical antitumor activity of liposomes coated with a glycosyl triazole glucose (GlcL-DOX) derivative as a potential strategy against breast cancer. The glucose-coating of liposomes enhanced the storage stability compared to PEG-coated liposomes, with the suitable retention of DOX encapsulation. The antitumor activity, using a 4T1 breast cancer mouse model, shows that GlcL-DOX controlled the tumor growth in 58.5% versus 35.3% for PEG-coated liposomes (PegL-DOX). Additionally, in the preliminary analysis of the GlcL-DOX systemic toxicity, the glucose-coating liposomes reduced the body weight loss and hepatotoxicity compared to other DOX-treated groups. Therefore, GlcL-DOX could be a promising alternative for treating breast tumors. Further studies are required to elucidate the complete GlcL-DOX safety profile. [ABSTRACT FROM AUTHOR]

Coffee is the food source of cafestol and kahweol (C&K), a pair of furanoditerpenoids that have antitumor, anticarcinogenic and anti-inflammatory properties. These diterpenes act on hallmarks of cancer such as resistance cell death, inducing angiogenesis, and activating migration & metastasis. Cafestol and kahweol have a wide antiproliferative and pro-apoptotic profile reported for different cell lines and reduce cancer cell resistance to antineoplastic drugs. Up to now, studies show that these diterpenes are the only bioactive compounds in coffee that show significant antitumor activity in specific cancer cell lines. The pharmacokinetics studies of C&K performed with different animal models demonstrate that they have a complex distribution and biotransformation. Besides the structure-activity relationship of C&K is not fully understood. This narrative review aims to highlight the potential of C&K in cancer chemoprevention and chemotherapy, pharmacokinetics, and the perspectives of the structure-activity relationship of these furanoditerpenoids. [ABSTRACT FROM AUTHOR]

In this study, X‐ray diffraction confirms the crystallization of aqua(1,10‐phenanthroline)(L‐serinato)copper(II) nitrate in the triclinic system (P‐1). Density functional theory calculations are used to assign the vibration bands of Cu2+ ion and phenanthroline (phen) and L‐serine (L‐ser) ligands obtained by Raman and Fourier‐transform infrared spectroscopy. Physical and analytical properties, evaluated by computational study utilizing CrystalExplorer software, show the prevalence of H···O/O···H interaction. Thermal analyses show that the complex is stable in the temperature interval of 300–390 K. For temperatures above 390 K, the elimination of coordinated water molecules (380–430 K), mass loss of serine (440–660 K), and material decomposition process above 660 K. The solubility of the complex in water reaches 21.4 mg mL−1 at 35 °C. Parameters of drug‐likeness and assessment of absorption, distribution, metabolism, and excretion (ADME) properties are calculated. The in vitro cytotoxic assays against the cancer cell line of the HCT‐116 type (human colorectal carcinoma) exhibits toxicity (IC50 = 1.88 µm and selectivity index of 2.17) for the complex. The results highlight the potential of ternary copper complexes such as [Cu(phen)(L‐ser)(H2O)]NO3 for anticancer drug development as attractive, efficient, and low‐cost materials. [ABSTRACT FROM AUTHOR]

Based on the simulated docking of Epidermal growth factor receptor inhibitors with known active small molecule compounds, computer-aided drug design technology was used to analyze key amino acid fragments and determine the active groups binding with key sites. Then, twelve novel analogues of oleanolic acid (OA) were synthesized by introducing active groups at the C-3 and C-28 positions of OA. The structures of these novel analogues were confirmed by NMR and MS. Furthermore, the antitumor activities of these novel analogues were evaluated by MTT assay. As a result, compounds I3 and II3 showed stronger cytotoxicity on tumor cells than positive controls. In conclusion, our study synthesized twelve novel analogues of OA and determined compounds I3 and II3 had better antitumor effect, which may be potential candidate compounds for tumor therapy. [ABSTRACT FROM AUTHOR]

As a novel and promising antitumor target, AXL plays an important role in tumor growth, metastasis, immunosuppression and drug resistance of various malignancies, which has attracted extensive research interest in recent years. In this study, by employing the structure-based drug design and bioisosterism strategies, we designed and synthesized in total 54 novel AXL inhibitors featuring a fused-pyrazolone carboxamide scaffold, of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions. Notably, compound 59 showed a desirable AXL kinase inhibitory activity (IC 50 : 3.5 nmol/L) as well as good kinase selectivity, and it effectively blocked the cellular AXL signaling. In turn, compound 59 could potently inhibit BaF3/TEL-AXL cell viability (IC 50 : 1.5 nmol/L) and significantly suppress GAS6/AXL-mediated cancer cell invasion, migration and wound healing at the nanomolar level. More importantly, compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency, in which we observed significant AXL phosphorylation suppression, and its antitumor efficacy at 20 mg/kg (qd) was comparable to that of BGB324 at 50 mg/kg (bid), the most advanced AXL inhibitor. Taken together, this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development. A class of novel AXL inhibitors has been discovered, in which compound 59 exhibited potent AXL inhibition, high kinase selectivity and significant in vivo anti-tumor efficacy with desirable pharmacokinetic profile. [Display omitted] [ABSTRACT FROM AUTHOR]

Natural products are essential sources of antitumor drugs. One such molecule, β -elemene, is a potent antitumor compound extracted from Curcuma wenyujin. In the present investigation, a series of novel 13,14-disubstituted nitric oxide (NO)-donor β -elemene derivatives were designed, with β -elemene as the foundational compound, and subsequently synthesized to evaluate their therapeutic potential against leukemia. Notably, the derivative labeled as compound 13d demonstrated a potent anti-proliferative activity against the K562 cell line, with a high NO release. In vivo studies indicated that compound 13d could effectively inhibit tumor growth, exhibiting no discernible toxic manifestations. Specifically, a significant tumor growth inhibition rate of 62.9% was observed in the K562 xenograft tumor mouse model. The accumulated data propound the potential therapeutic application of compound 13d in the management of leukemia. [ABSTRACT FROM AUTHOR]

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In this study, crude polysaccharide of Sargassum angustifolium (PSA) was extracted with an extraction efficiency of 7.14% and a molecular weight of 1831.55 kDa. Then two fractions PSA-1 and PSA-2 with yields of 38.12% and 61.07% and molecular weights of 809.2 and 644.1 kDa were obtained by a DEAE column. Based on the results, fucose (40.41%), glucose (19.30%) and galactose (27.13%) were identified as the dominant monosaccharides in polysaccharides. The IC50 value of DPPH free radical scavenging by PSA, PSA-1 and PSA-2 was 0.32, 0.24 and 0.19 mg/mL, respectively. Also, the IC50 value of ABTS radical scavenging by PSA, PSA-1 and PSA-2 was estimated at about 0.24, 0.17 and 0.14 mg/mL, respectively. According to the results, Fraction PSA-2 had the highest antioxidant activity. In this study, the ability of all fractions to inhibit Hela cancer cells was determined, and the most significant effect was observed by fraction PSA-2. The inhibition rate of HeLa cells by PSA and PSA-1 and PSA-2, at a concentration of 0.4 mg/mL was about 40.56% and 51.70% and 70.81%, respectively. Therefore, S. angustifolium polysaccharide, especially fraction PSA-2, can be introduced as a natural compound with anticancer and antioxidant activity for food and pharmaceutical applications. [ABSTRACT FROM AUTHOR]

Bimetallic nanoparticles (BMNPs) combine unique and synergistic properties of two metals, allowing new specific applications. In this study, bimetallic AuFe nanoparticles and their conjugates with methotrexate (MTX) were obtained with an environmentally safe method of metal-vapor synthesis. The composition and electronic structure of the particles were investigated with X-ray photoelectron spectroscopy (XPS), energy dispersive X-ray (EDX) spectrum and X-ray absorption spectroscopy (XANES and EXAFS). The effects of BMNP-MTX conjugates on human primary cells and tumor cell lines were evaluated with neutral red uptake and MTT in vitro cytotoxicity assays. Bright-field microscopy analyses of tumor spheroid size and evaluations of tumor spheroid vitality based on SFDA AM staining were carried out. In vitro assays for an antibacterial activity evaluation of the generated samples were performed. The influence of BMNP-MTX on cytokine production with normal leukocytes was assessed using ELISA. X-ray analyses of the samples demonstrated that gold was in the ground state Au0 as well as Au+ and Au3+ states are present in small quantities, whereas iron existed as a mixture of non-histometric oxides with states close to Fe2+ and Fe3+. The modification of the AuFe system with MTX is accompanied by a threefold increase in the relative proportion of the Au+ state. BMNP-MTX conjugates demonstrated significant antitumor activity compared to the drug alone, which proves the ability of the generated nanoconjugates to improve the effectiveness of MTX therapy. This was confirmed by a marked reduction in the size and vitality of AuFe-MTX-treated 3D tumor spheroids. In addition to their selective antitumor activity, AuFe-MTX exhibited moderate antibacterial activity and induced sample-specific cytokine production with normal human leukocytes—which points to an immunostimulatory potential. The present findings indicate important and diverse biological properties of BMNP-MTX conjugates and thus highlight perspectives for their biomedical applications and new immune-specific abilities. [ABSTRACT FROM AUTHOR]

Background: The effects of nanosized boron phosphate-filled sodium alginate composite gel (SA/BP) on the biological characteristics of three types of glioblastoma multiforme (GBM) cells (C6, U87MG and T98G) were examined in this study. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay was used to determine the cytotoxicity of the composite gel on GBM, which was then compared to L929 healthy cells. Furthermore, wound healing, apoptosis, and colony formation capacities were evaluated. The investigation revealed that the SA/BP composite gel was successful in all GBM cells and could be used as a treatment agent for GBM and/or other invasive cancer types. Methods and results: According to the results, the SA/BP composite gel had no effect on healthy fibroblast cells but had a lethal effect on all glioblastoma cells. Additionally, the wound healing method was used to examine the effect of the SA/BP composite gel on cell migration. It was discovered that the wound closed in 24 h in untreated control group cells, while the SA/BP composite gel closed up to 29.62%, 26.77% and 11.31% of the wound for C6, U87MG and T98G cell lines respectively. SA/BP significantly reduced cell migration in cancer cells. The effect of the generated SA/BP composite gel on cell colony development was assessed using a colony formation assay, and the cells reduced colony formation for all GBMs. It was roughly 45% for 24 h and 30% for 48 h when compared to the control group for C6 cells, 33%(24 h) and 40%(48 h) for U87MG cells, 40%(24 h) and 43%(48 h) for T98G cells. DAPI(4′,6-Diamidino-2-phenylindole) and JC-1(5,5′,6,6′-Tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine, iodide) staining to evaluate apoptosis revealed that the SA/BP composite gel dramatically enhanced the frequency of all GBMs undergoing apoptosis. Conclusions: In line with experimental findings, it was observed that the SA/BP composite gel system did not affect healthy fibroblast cells but had a cytotoxic effect on glioblastoma cells, significantly reduced cell migration and colony-forming capacity of cells, and significantly increased apoptosis and depolarization of cell membranes. Based on all these findings, it can be said that SA/BP composite gel has cytotoxic, antiproliferative and antiapoptotic effects on different glioblastoma cells. [ABSTRACT FROM AUTHOR]

Sixteen ceanothane-type triterpenoids, including four new compounds—hovendulcisic acids A–D (1–4) —were purified from the stems of Hovenia dulcis Thunb. The structures of 1–4 were confirmed by comprehensive means including ECD and quantum chemical calculations. Putative biosynthetic pathways of 1–16 were proposed, and 3, 5, and 15 exhibited antitumor activity on A549 and MDA-MB-231 cells.

Summary: Background: Current approved chimeric antigen receptor (CAR) T-cell products are autologous cell therapies that are costly and poorly accessible to patients. We aimed to evaluate the safety and antitumor activity of a novel off-the-shelf anti-CD19 CAR-engineered allogeneic double-negative T cells (RJMty19) in patients with relapsed/refractory large B-cell lymphoma. We report the results from a first-in-human, open-label, single-dose, phase 1 study of allogeneic CD19-specific CAR double-negative T (CAR-DNT) cells. Methods: Eligibility criteria included the presence of measurable lesions, at least 2 lines of prior immunochemotherapy, and an ECOG score of 0–1. We evaluated four dose levels (DL) of RJMty19 in a 3 + 3 dose-escalation scheme: 1 × 106, 3 × 106, 9 × 106 and 2 × 107 CAR-DNT cells per kilogram of body weight. All patients received lymphodepleting chemotherapy with fludarabine and cyclophosphamide. The primary endpoints were dose-limiting toxicities (DLTs), incidence of adverse events (AEs), and clinically significant laboratory abnormalities. Secondary endpoints included evaluation of standard cellular pharmacokinetic parameters, immunogenicity, objective response rates (ORR), and disease control rate (DCR) per Lugano 2014 criteria. Findings: A total of 12 patients were enrolled between 22 July 2022 and 27 July 2023. Among these patients, 66% were classified as stage IV, 75% had an IPI score of 3 or higher, representing an intermediate risk or worse. The maximum tolerated dose was not reached because no DLT was observed. Four patient experienced grade 1 or 2 cytokine release syndrome and dizziness. The most common AEs were hematologic toxicities, including neutropenia (N = 12, 100%), leukopenia (N = 12, 100%), lymphopenia (N = 10, 83%), thrombocytopenia (N = 6, 50%), febrile neutropenia (N = 3, 25%), and anemia (N = 3, 25%). Seven subjects died till the cut-off date, five of them died of disease progression and two of them died of COVID 19. In all patients (N = 12), the ORR was 25% and CRR was 8.3%. DL1 and DL2 patients benefited less from the therapy (ORR: 17%, N = 1; DCR: 33%, N = 2). However, all DL3 patients achieved disease control (N = 3, 100%), and all DL4 patients achieved objective response (N = 3, 100%). Interpretation: Our results demonstrate that CD19-CAR-DNT cells appear to be well tolerated with promising antitumor activity in LBCL patients. Further study of this product with a larger sample size is warranted. This phase 1 study is registered on clinicaltrials.gov (NCT05453669). Funding: Wyze Biotech. Co., Ltd.

Abstract Background Liver‐resident natural killer (lr‐NK) cells are distinct from conventional NK cells and exhibit higher cytotoxicity against hepatoma via tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL). However, the mechanism by which partial hepatectomy (PH) significantly suppresses TRAIL expression in lr‐NK cells remains unclear. Methods This study aimed to investigate the PH influence on the function and characteristics of liver‐resident NK (lr‐NK) cells using a PH mouse model. Results Here, we report that PH alters the differentiation pattern of NK cells in the liver, and an aryl hydrocarbon receptor (AhR) molecule is involved in these changes. Treatment with the AhR agonist 6‐formylindolo[3,2‐b]carbazole (FICZ) inhibited the maturation of NK cells. FICZ increased the immature subtype proportion of NK cells with high TRAIL activity and decreased the mature subtype of NK cells with low TRAIL activity. Consequently, FICZ increased the expression of TRAIL and cytotoxic activity of NK cells in the liver, and this effect was confirmed even after hepatectomy. The participation of AhR promoted FoxO1 expression in the mTOR signaling pathway involved in the maturation of NK cells, resulting in TRAIL expression. Conclusion Our findings provide direct in‐vivo evidence that partial hepatectomy affects lrNK cell activity through NK cell differentiation in the liver. Perioperative therapies using an AhR agonist to improve NK cell function may reduce the recurrence of hepatocellular carcinoma after hepatectomy.

A novel lectin (termed PML) was purified from fruiting bodies of the edible mushroom Phellodon melaleucus (division Basidiomycota) by ion exchange, hydrophobic interaction, and gel filtration chromatographies, with overall titer recovery ~60 % and 20-fold purification. PML displayed hemagglutination activity 13319 units/mg toward rabbit erythrocytes. SDS-PAGE and gel filtration analyses revealed that PML is a homodimeric lectin with a molecular weight of 28.8 kDa. PML hemagglutination activity was not inhibited by various simple sugars or their derivatives, but was enhanced by cations Ca2+, Mg2+, Zn2+, and Cu2+. The activity was stable in pH range 6–9 and in the temperature range 20–60 °C. Circular dichroism (CD) spectroscopic analysis showed that PML was composed primarily of β-sheets with low α-helix content. In a B16 melanoma mouse model, PML treatment significantly inhibited tumor growth, and increased cytokine IL-10 content. Our findings suggest that PML is a potential anticancer therapeutic agent.

As medical cannabis becomes legal in more states, cancer patients are increasingly interested in the potential utility of the ancient botanical in their treatment regimen. Although eager to discuss cannabis use with their oncologist, patients often find that their provider reports that they do not have adequate information to be helpful. Oncologists, so dependent on evidence-based data to guide their treatment plans, are dismayed by the lack of published literature on the benefits of medical cannabis. This results largely from the significant barriers that have existed to effectively thwart the ability to conduct trials investigating the potential therapeutic efficacy of the plant. This is a narrative review aimed at clinicians, summarizing cannabis phytochemistry, trials in the areas of nausea and vomiting, appetite, pain and anticancer activity, including assessment of case reports of antitumor use, with reflective assessments of the quality and quantity of evidence. Despite preclinical evidence and social media claims, the utility of cannabis, cannabinoids or cannabis-based medicines in the treatment of cancer remains to be convincingly demonstrated. With an acceptable safety profile, cannabis and its congeners may be useful in managing symptoms related to cancer or its treatment. Further clinical trials should be conducted to evaluate whether the preclinical antitumor effects translate into benefit for cancer patients. Oncologists should familiarize themselves with the available database to be able to better advise their patients on the potential uses of this complementary botanical therapy.

Background/aimThe majority of targeted therapies are focused on BRCA mutations, homologous recombination repair deficiency, and BRCA wild-type platinum-sensitive recurrent ovarian cancer. There is a growing need for platinum-resistant patients without BRCA mutations. Herein, we conducted a phase II multicenter study evaluated the efficacy and safety of bortezomib plus pegylated liposomal doxorubicin (PLD) in patients with BRCA wild-type platinum-resistant recurrent ovarian cancer (NCT03509246).Patients and methodsOvarian cancer patients with wild-type BRCA who experienced platinum-resistant recurrence after three or less prior treatment cycles from three Institutions were included. All patients received bortezomib, 1.3 mg/m2 subcutaneously (days 1, 4, 8, and 11), and PLD, 40 mg/m2 intravenously (day 4), every 4 weeks. The primary endpoint was best objective response rate (ORR), and secondary endpoints included disease control rate, progression-free survival (PFS), overall survival, and safety. Targeted sequencing was performed to evaluate biomarkers and their potential association with response to treatment.ResultsThe trial was terminated after 23 patients were recruited because of slow accrual. The median follow-up was 29.5 months. The overall ORR was 8.7% (2/23); partial response was observed in two patients. The median duration of response was 10.5 months, and median PFS was 2.9 months. Treatment-related adverse events (TRAEs) of grade 3/4 were reported in 43.5% of patients. One patient who exhibited TRAEs discontinued treatment. However, grade 4/5 TRAEs were not observed. Mutations in TP53 and CDK12 were detected in 67% (14/21) and 24% (12/21) of patients, respectively. Two patients with partial response harbored mutations in genes related to homologous recombination repair deficiency, including BRCA2, ATM, and CDK12.ConclusionThe combination of bortezomib and PLD was well tolerated; however, antitumor activity was not sufficient to warrant further investigation in ovarian cancer.

Stimulus-responsive materials hold significant promise for antitumor applications due to their variable structures and physical properties. In this paper, a series of peptides with a responsive viologen derivative, Pep-CnV (n = 1, 2, 3) were designed and synthesized. The process and mechanism of the interaction were studied and discussed. An ultraviolet–visible (UV) spectrophotometer and fluorescence spectrophotometer were used to study their redox responsiveness. Additionally, their secondary structures were measured by Circular Dichroism (CD) in the presence or absence of the reductant, Na2SO3. DPPC and DPPG liposomes were prepared to mimic normal and tumor cell membranes. The interaction between Pep-CnV and biomembranes was investigated by the measurements of surface tension and cargo leakage. Results proved Pep-CnV was more likely to interact with the DPPG liposome and destroy its biomembrane under the stimulus of the reductant. And the destruction increased with the length of the hydrophobic tail chain. Pep-CnV showed its potential as an intelligent antitumor agent.

Sporisorium reilianum is an important biotrophic pathogen that causes head smut disease. Polysaccharides extracted from diseased sorghum heads by Sporisorium reilianum exhibit significant medicinal and edible value. However, the structure and biological activities of these novel polysaccharides have not been explored. In this study, a novel polysaccharide (WM-NP’-60) was isolated and purified from the fruit bodies of S. reilianum and aimed to explore the structural characteristics and substantial antioxidant and antitumor properties of WM-NP’-60. Monosaccharide composition determination, periodate oxidation-Smith degradation, 1D/2D-NMR analysis, and methylation analysis revealed that WM-NP’-60 consisted mainly of β-1,6-D-Glcp, β-1,3-D-Glcp, and β-1,3,6-D-Glcp linkages. The antioxidant assays demonstrated that WM-NP’-60 exhibited great activities, including scavenging free radicals, chelating ferrous ions, and eliminating reactive oxygen species (ROS) within cells. The HepG2, SGC7901, and HCT116 cells examined by transmission electron microscopy (TEM) revealed typical apoptotic bodies. Therefore, a novel fungal polysaccharide (WM-NP’-60) was discovered, extracted, and purified in this experiment, with the aim of providing a reference for the development of a new generation of food and nutraceutical products suitable for human consumption.

Selenium, zinc, copper, and manganese are essential components of antioxidant enzymes involved in the elimination of reactive oxygen species (ROS). Given that cancer cells produce high levels of ROS and the accumulation of ROS can lead to cell death, cancer cells may be susceptible to strategies that reduce ROS elimination. In this work, we prepared several artificial diets that contained normal carbohydrate, protein, and lipid levels but lacked selenium, zinc, copper, or manganese. The anticancer activity of these diets was examined in a metastatic ovarian cancer model, established by injecting ID8 Trp53−/− murine ovarian cancer cells into the peritoneal cavity of C57BL/6JRj mice. Treatments started 15 days later and consisted of replacing a normal diet with one of the artificial diets for several weeks. A significant improvement in mice survival was observed when the normal diet was replaced with the selenium-free diet. Diets lacking zinc, copper, or manganese showed no significant impact on mice survival. All diets were very well tolerated. The anticancer efficacy of a diet lacking selenium was confirmed in mice with metastatic colon cancer and in mice with metastatic triple-negative breast cancer. These results suggest that diets lacking selenium hold potential for the treatment of metastatic cancers.

In this work, we show the in vitro anticancer potential of surgical wires, obtained from zinc (ZnMg0.004) or magnesium (MgCa0.7) alloys by spatial technology comprising casting, extrusion, and final drawing processes. We also present the selective anticancer effects of applied soluble multilayer nanocoatings of zinc and magnesium onto titanium surfaces using the pulse laser deposition method. In the latter, the titanium samples were produced via 3D printing using the selective laser melting method and coated with various combinations of zinc and magnesium layers. For cytotoxicity studies, human dental pulp-derived stem cells (hDPSCs) and human osteosarcoma SaOS-2 cell line were used as representatives of healthy and cancer cells. Cells were examined against the 0.3–3.0 cm2/mL material extract ratios obtained from experimental and steel surgical wires, the latter being the current clinical industry standard. The MgCa0.7 alloy wires were approx. 1.5 times more toxic to cancer cells at all examined extract ratios vs. the extracts from steel surgical wires that exhibited comparable toxicity towards healthy and cancer cells. The ZnMg0.004 alloy wires displayed increased toxicity towards cancer cells with decreasing extract ratios. This was also reflected in the increased anticancer effectiveness, calculated based on the viability ratio of healthy cells to cancer cells, from 1.1 to 4.0 times. Healthy cell viability remained at 80–100%, whereas cancer cell survival fluctuated at 20–75%, depending on the extract ratio. Furthermore, the culture of normal or cancer cells on the surface of Zn/Mg-coated titanium allowed us to select combinations of specific coating layers that yielded a comparable anticancer effectiveness to that observed with the experimental wires that ranged between 2 and 3. Overall, this work not only demonstrates the substantial anticancer properties of the studied wires but also indicates that similar anticancer effects can be replicated with appropriate nanocoatings on titanium samples. We believe that this work lays the groundwork for the future potential development of the category of new implants endowed with anticancer properties.