Anti-cancer agents in medicinal chemistry最新文献

{"title":"A Systematic Review and Meta-analysis on the Safety and Efficacy of CAR T Cell Therapy Targeting GPRC5D in Patients with Multiple Myeloma: A New Insight in Cancer Immunotherapy.","authors":"Behrouz Robat-Jazi, Mehrdad Mahalleh, Mohsen Dashti, Negar Nejati, Mahsa Ahmadpour, Erfan Alinejad, Shiva Mohammadi, Parsa Lorestani, Amir Ali Hamidieh, Mohammad Amin Habibi, Farhad Jadidi-Niaragh","doi":"10.2174/0118715206350342241224073809","DOIUrl":"10.2174/0118715206350342241224073809","url":null,"abstract":"<p><strong>Background: </strong>Despite ongoing advances and introducing innovative therapeutic approaches for the treatment of multiple myeloma (MM), relapses are common, with low overall survival rates. G protein-coupled receptor, class C, group 5, and member D (GPRC5D) has been expressed in several myeloma cell lines and has demonstrated encouraging outcomes results in <i>in-vitro</i> studies as a potential target for immunotherapies.</p><p><strong>Objective: </strong>We aimed to investigate the safety and efficacy of GPRC5D-targeted CAR T cell therapies in MM patients.</p><p><strong>Methods: </strong>On August 24, 2023, the databases of PubMed, Scopus, Embase, and Web of Science were systematically searched for pertinent studies. After completing a two-step title/abstract and full-text screening process, the eligible studies were included.</p><p><strong>Results: </strong>Following the screening of 107 articles, four studies of 130 multiple myeloma patients treated with GPRC5D-targeted CAR T-cell therapy were included. The meta-analyses showed an ORR of 87% (95% CI [81- 93%]), with 74% (95% CI [65-73%]) for those with prior BCMA-targeted therapy and 88% (95% CI [78-99%]) for those without. PR was 25%, VGPR 33%, and CR/sCR 48%, with 65% achieving MRD-negativity. In terms of safety, hematologic AEs were common, with anemia reported in 86% of patients. Non-hematologic common AEs included CRS (83%, 5% grade ≥3) and hypocalcemia (63%, 10% grade ≥3). No significant publication bias was detected.</p><p><strong>Conclusion: </strong>GPRC5D is an active and safe target that shows promising results in the treatment of relapsed and/or refractory (R/R) MM and heavily pretreated patients.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"1017-1028"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143121979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the Therapeutic Potential of Trigonelline: A Promising Approach in Cancer Prevention and Treatment.","authors":"Yufei Zhu, Danni Ding, Fang Shen, Fangyuan Liu, Yang Yu, Fengjuan Han","doi":"10.2174/0118715206363456250226061713","DOIUrl":"10.2174/0118715206363456250226061713","url":null,"abstract":"<p><p>With the development of herbal medicine, more and more chemical extracts isolated from natural herbs are being used to treat cancer, and herbal monomers play an important role in treating tumors. There is no doubt that these substances have a powerful ability to address the growing incidence of cancer. Among them, Trigonelline, due to its anti-tumor, hypoglycemic, hypolipidemic, antioxidant, and aphrodisiac properties, has been comprehensively studied for its therapeutic potential. However, there is a lack of a complete and specific review of Trigonelline research. Regarding the information mentioned before, this paper summarizes and describes the literature related to the response mechanisms and therapeutic potential of Trigonelline. This review describes the effects of Trigonelline in inhibiting tumor growth and metastasis, reducing the toxicity of chemotherapeutic agents, decreasing oxidative stress, increasing the sensitivity type of chemotherapeutic agents, and reversing drug resistance. On account of the merits of low cost, safety and efficacy, and few toxic side effects, Trigonelline has the potential to become a new and valuable drug. Furthermore, the in-depth study of this natural substance is yet to be further developed. In addition, by exploiting it more extensively, it is expected to be an effective addition to cancer treatment. We can expect that in the future more and more herbal extracts can be used in clinical practice to prolong the survival and improve the quality of life of patients.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"1175-1187"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selected Metal (Au, Ag, and Cu) Complexes of N-heterocyclic Ligands as Potential Anticancer Agents: A Review.","authors":"Meshal Alshamrani","doi":"10.2174/0118715206331002241119145651","DOIUrl":"10.2174/0118715206331002241119145651","url":null,"abstract":"<p><p>Nitrogen-based organic heterocyclic compounds are an important source of therapeutic agents. About 75% of drugs approved by the FDA and currently available in the market are N-heterocyclic organic compounds. The N-heterocyclic organic compounds like pyridine, indole, triazoles, triazine, imidazoles, benzimidazoles, quinazolines, pyrazoles, quinolines, pyrimidines, porphyrin, etc. have demonstrated significant biological activities. These heterocyclic organic compounds also coordinate with various metal ions and form coordination compounds. Most of them have shown improved biological activities. The research on the metal complexes of these compounds reported their significant biological activities. N-heterocyclic-based metal complexes showed outstanding anticancer activities against different cancer cell lines, including VEGFR-2, HT-29, MDA-MB-231, MCF-7 K562, A549, HepG2, HL60, A2780, WI-38, Colo-205, PC-3, and other cancer cell lines. Some of these compounds showed better anticancer activity than cisplatin. In this review, we summarized the anticancer properties of N-heterocyclic-based gold (Au), silver (Ag), and copper (Cu) complexes and explored the mechanisms of action and potential structure-activity relationships (SAR) of these complexes. Our goal is to assist researchers in designing highly potent N-heterocyclic-based Au, Ag, and Cu complexes for the potential treatment of various cancers.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"729-740"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Royal Jelly's Strong Selective Cytotoxicity Against Lung Malignant Cells and Macromolecular Alterations in Cells Observed by FTIR Spectroscopy.","authors":"Ferhunde Aysin","doi":"10.2174/0118715206355400241112084611","DOIUrl":"10.2174/0118715206355400241112084611","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction/objective: &lt;/strong&gt;Several nutraceuticals, food, and cosmetic products can be developed using royal jelly. It is known for its potential health benefits, including its ability to boost the immune system and reduce inflammation. It is rich in vitamins, minerals, and antioxidants, which can improve general health. Royal jelly (RJ) is also being studied as a potential therapeutic agent for cancer and other chronic diseases. It is effective in reducing tumor growth and stimulating immunity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this study, we investigated the effects of royal jelly on cancerous A549 cells and healthy MRC-5 cells at various doses ranging from 1.25 to 10 mg/mL. Royal jelly's anti-proliferative effect was evaluated by MTT and SRB assay for 48 h. The induction of necrosis and apoptosis was assessed by flow cytometry as well. The relative amounts of major molecules in Royal jelly were determined by FTIR spectroscopy to identify key functional groups and molecular structures. In addition, this technique was used for the first time to detect changes in the macromolecular composition of lung cells treated with royal jelly. Thus, it provided insights into the relative abundance of proteins, lipids, and carbohydrates, which could correlate with their bioactive properties.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The antiproliferative effect of Royal jelly was found to be selective on A549 cells in a dose-dependent manner with an IC&lt;sub&gt;50&lt;/sub&gt; of 9.26 mg/mL, with no cytotoxic effects on normal MRC-5 cells. Moreover, Royal jelly induced predominantly necrotic cell death in A549 cells, %39.10 at 4 mg/mL and %57.88 at 10 mg/mL concentrations. However, the necrosis rate in MRC-5 cells was quite low, at 9.16% and 20.44% at the same doses. Royal jelly showed dose-dependent selective cytotoxicity toward A549 cells, whereas it exhibited no apparent cytotoxicity in MRC-5 cells. In order to identify the biomolecular changes induced by royal jelly, we used two unsupervised chemometric pattern recognition algorithms (PCA and HCA) on the preprocessed sample FTIR spectra to determine the effects of royal jelly on cell biochemistry. According to PCA and HCA results, RJ treatments especially affected biomolecules in A549 cells. The total spectral band variances in the PCA loading spectra were calculated for understanding biomolecular alterations. These plots revealed profound changes in the lipid, protein, and nucleic acid content of RJ-applied lung cells, primarily identifying RJ and H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt; treated groups for A549 cells.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Ultimately, the selective cytotoxicity of royal jelly toward A549 cancerous cells suggests that royal jelly may be a promising therapeutic agent for identifying innovative lung cancer treatment strategies. Additionally, understanding the molecular alterations induced by royal jelly could guide the development of novel cancer treatments that exploit its bioactive properties.","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"750-764"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chlorogenic Acid Ameliorates CCl₄-induced Liver Fibrosis by Modulating the PI3K/AKT/mTOR Autophagy Pathway.","authors":"Amr Negm, Amira Afifi El-Neanaey, Abada El Sayed Khadr, Maher Abd El Naby Kamel, Abd El-Hamid Abdo Ismail, Ibrahim El Tantawy El Sayed, Wael Sobhy Darwish, Mabrouk Attia Abd Eldaim, Raghda Sobhy Okaz, Mohamed Hamdy Bahr, Nihal Almuraikhi, Nermine Beshara, Tamer Mohamed Shawky, Ezat A Mersal","doi":"10.2174/0118715206357043250116063202","DOIUrl":"10.2174/0118715206357043250116063202","url":null,"abstract":"<p><strong>Background: </strong>Liver fibrosis represents a serious risk to global health by impairing quality of life and elevating the chances of hepatocellular carcinoma, while the intricate role of autophagy can either alleviate or worsen fibrosis depending on its functioning.</p><p><strong>Objective: </strong>Herein, we aimed to investigate the therapeutic effect of chlorogenic acid in CCl₄-induced hepatic fibrosis and explored the autophagy pathway as the possible molecular target of chlorogenic acid.</p><p><strong>Methods: </strong>Rats were injected with carbon tetrachloride (1ml/kg) to induce liver fibrosis for 10 weeks. In the current study, the liver fibrosis rats were treated daily with chlorogenic acid (20, 40, and 60 mg/kg) for 30 days. Liver function tests, renal function tests, lipid peroxidation, antioxidant enzyme, anti-inflammatory NF-κB level, and autophagy pathway parameters (PI3K, AKT, mTOR, LC3, and Beclin-1) were assessed.</p><p><strong>Results: </strong>CCl₄ elevated serum AST and ALT activity, and hepatic malondialdehyde, PI3K, AKT, and mTOR expressions. It decreased LC3, Beclin-1 expression, and hepatic glutathione level. The results indicated that chlorogenic acid treatment ameliorated the hepatic functions. It declined serum AST and ALT activities, improved hepatic GSH concentration, decreased lipid peroxidation, and downregulated PI3K, AKT, and mTOR protein expressions in hepatic tissue. Moreover, chlorogenic acid increased the hepatic expression of LC3 and Beclin-1. It also significantly decreased NF-kB expression.</p><p><strong>Conclusion: </strong>Chlorogenic acid showed promise in reducing liver damage in rats caused by CCl₄ by influencing the autophagy process and adjusting levels of antioxidant and inflammatory markers.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"913-920"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Notice to \"Anti-proliferative, Morphological and Molecular Docking Studies of New Thiophene Derivatives and their Strategy in Ionic Liquids Immobilized Reactions\".","authors":"Rafat M Mohareb, Sayeed Mukhtar, Humaira Parveen, Mahmoud A Abdelaziz, Ensaf S Alwan","doi":"10.2174/1871520625999250311114343","DOIUrl":"10.2174/1871520625999250311114343","url":null,"abstract":"<p><p>We regret to inform you that the article titled \"Anti-proliferative, Morphological and Molecular Docking Studies of New Thiophene Derivatives and their Strategy in Ionic Liquids Immobilized Reactions,\" published in Volume 24, Issue 9, 2024 of Anti-Cancer Agents in Medicinal Chemistry (10.2174/0118715206262307231122104748), is being retracted. After a thorough investigation, it was found that there was potential data manipulation in the spectral data provided in the manuscript. The integrity of the data presented in the study could not be verified, leading to the decision to retract the article. We apologize for any inconvenience this may have caused and appreciate your understanding in this matter. Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure, or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":"25 17","pages":"1369"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Path to the Formation Mechanism of Propolis Nanoparticles, their Cytotoxicity on 3T3 Fibroblasts, Metastatic Murine B16F10 Cells, and their <i>In vivo</i> Irritability in Animals.","authors":"Jeimmy Gonzalez-Masis, Rodolfo J Gonzalez-Paz, Yendry Regina Corrales Urena, Simon Guerrero, Sara Gonzalez-Camacho, Nohelia Mora-Ugalde, Monica Baizan-Rojas, Randall Loaiza, Jose Roberto Vega-Baudrit, Jorge M Cubero-Sesin","doi":"10.2174/0118715206316231250218063957","DOIUrl":"10.2174/0118715206316231250218063957","url":null,"abstract":"<p><strong>Background: </strong>Natural products, such as propolis, are an important source of biologically active compounds with the potential to treat health disorders. Propolis is a well-known waxy resin recognized for its antimicrobial, immunomodulatory, and cytotoxic effects.</p><p><strong>Objective: </strong>In this study, we aimed to clarify the formation mechanism of propolis nanoparticles from the perspective of their stability and chemical composition. By evaluating the light absorption behaviour of the nanoparticles formed in different media and quantifying the polyphenols, we show that they are superficially hydrophobic nanoparticles with the capacity to encapsulate some polar compounds.</p><p><strong>Methods: </strong>Biological activity was evaluated by <i>in vitro</i> cell viability performed on NIH/3T3 fibroblasts incubated with 10, 100, and 1000 μg/mL of propolis nanoparticles for 48 hours.</p><p><strong>Results: </strong>The results show that nanoparticles are cytocompatible, with a proliferation effect. In contrast, the results of the viability of metastatic murine B16F10 cells indicate that a dose with a concentration of 5 μg/mL in the cell culture media is sufficient to stop the abnormal cell growth, having an antitumor effect. This effect might be related to the flavonoids present in the propolis nanoparticles. In vivo dermal irritability tests on New Zealand rabbits show that propolis nanoparticles' aqueous dissolution was non-irritant.</p><p><strong>Conclusion: </strong>According to the results obtained from this study, reducing the size of raw propolis down to nanoparticles and dispersing them in water solvents enhance its positive effects. The superficially hydrophobic propolis nanoparticles encapsulate active compounds such as polyphenols and flavonoids, which also confirms their ability to generate selective effects on the cells, depending on their nature.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"1331-1341"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut Microbiota and the Gut-liver Axis in Hepatocellular Carcinoma: A Comprehensive Review of Pathogenesis and Therapeutic Strategies.","authors":"Satyam Yadav, Ranjeet Kumar","doi":"10.2174/0118715206364200250304034753","DOIUrl":"10.2174/0118715206364200250304034753","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is among the most prevalent and fatal cancers globally. The gut-liver axis, involving intricate interactions between gut microbiota and the liver, has emerged as a critical pathway in HCC development. This review comprehensively examines the molecular mechanisms by which gut microbiota contribute to hepatocarcinogenesis. It discusses factors that either protect against or promote HCC, such as bacterial translocation, and explores the biological processes that drive carcinogenesis, while addressing clinical and pathophysiological complexities. Special attention is given to the role of toll-like receptors (TLRs) and inflammation in liver cells, where microbial components trigger changes in TLR activation, leading to increased inflammation and fibrosis. Additionally, the review covers obesity-related HCC, highlighting the impact of gut microbiota alterations on this cancer type. It critically assesses current literature on therapeutic interventions targeting gut microbiota in HCC, focusing on strategies like probiotics and antibiotics that could modulate microbial composition to prevent HCC progression. The review also explores gut microbiota-derived biomarkers for early detection and monitoring of HCC and discusses personalized therapies based on individual gut-liver interactions. Finally, it identifies research gaps and suggests future studies to deepen understanding of how gut microbiota can be leveraged as an adjunct therapy in HCC. Overall, the review underscores the pivotal role of gut microbiota in HCC pathogenesis and treatment, pointing to microbiome modulation as a promising therapeutic avenue.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"1287-1301"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Active Phytochemicals to Inhibit Signal Transducer and Activator of Transcription 5A (STAT5A) Dimerization for Prostate Cancer Therapy: An <i>In Silico</i> Approach.","authors":"Shalaka R Patki, Shyam S Pottabathula, Arehalli S Manjappa, Alagarsamy Veerachamy, Murugesan Sankaranarayanan, Mohammed Muzaffar-Ur-Rehman, Ahmad Salawi, Sunil T Galatage, John I Disouza, Vinyas Mayasa","doi":"10.2174/0118715206367609250329195533","DOIUrl":"10.2174/0118715206367609250329195533","url":null,"abstract":"<p><strong>Background: </strong>The Src Homology 2 (SH2) domain, the most conserved region of STAT5a/b (aa 573-712), is crucial for receptor-specific recruitment and STAT5 dimerization, making it a therapeutic target in prostate cancer (PCa).</p><p><strong>Objectives: </strong>This study explored the SH2 domain of STAT5a and carried out the identification of natural STAT5a inhibitors.</p><p><strong>Methods: </strong>Using template-based homology modeling, we constructed the structure of human STAT5a (VP1P) and compared it with its 3D crystal of the STAT5a protein obtained from the RCSB database and the model generated by the AlphaFold database. In this study, we carried out molecular docking studies using AutoDock Vina on the top 500 natural compounds identified through a pharmacophore search of the ZINC database using ZINCPharmer. Furthermore, the top ten compounds with the highest binding energies were evaluated for their drug-likeness and ADMET properties using SWISS ADME and ProTox-II, followed by 100 ns molecular dynamics (MD) simulations using the Desmond module of the Schrodinger suite.</p><p><strong>Results: </strong>Docking studies revealed Pedunculagin (-10.5 kcal/mol), Folic acid (-10.1 kcal/mol), Chebulinic acid (-10.0 kcal/mol), Chebulagic acid (-9.8 kcal/mol), and Oleandrin (-9.8 kcal/mol) as the top candidates, compared to the STAT5 inhibitor (Phase-II Clinical Trial) (-8.5 kcal/mol). ADMET analysis confirmed their safety profiles. MD simulations showed stable protein-ligand complexes, with all compounds interacting with the conserved Arg638 residue at the active site, similar to the STAT5 inhibitor.</p><p><strong>Conclusion: </strong>Pedunculagin demonstrated the strongest binding energy and stability, making it a promising candidate for further development as a novel lead compound to disrupt STAT5a/b dimerization in PCa therapy.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"1456-1472"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MG132-mediated Suppression of the Ubiquitin-proteasome Pathway Enhances the Sensitivity of Endometrial Cancer Cells to Cisplatin.","authors":"Zhanhu Zhang, Yiqian Ding","doi":"10.2174/0118715206343550240919055701","DOIUrl":"10.2174/0118715206343550240919055701","url":null,"abstract":"<p><strong>Background: </strong>Tumor cell resistance to cisplatin is a common challenge in endometrial cancer chemotherapy, stemming from various mechanisms. Targeted therapies using proteasome inhibitors, such as MG132, have been investigated to enhance cisplatin sensitivity, potentially offering a novel treatment approach.</p><p><strong>Objective: </strong>The aim of this study was to investigate the effects of MG132 on cisplatin sensitivity in the human endometrial cancer (EC) cell line RL95-2, focusing on cell proliferation, apoptosis, and cell signaling.</p><p><strong>Methods: </strong>Human endometrial cancer RL95-2 cells were exposed to MG132, and cell viability was assessed in a dose-dependent manner. The study evaluated the effect of MG132 on cisplatin-induced proliferation inhibition and apoptosis, correlating with caspase-3 activation and reactive oxygen species (ROS) upregulation. Additionally, we examined the inhibition of the ubiquitin-proteasome system and the expression of pro-inflammatory cytokines IL-1β, IL-6, IL-8, and IL-13 during MG132 and cisplatin co-administration.</p><p><strong>Results: </strong>MG132 exposure significantly reduced cell viability in a dose-dependent manner. It augmented cisplatin- induced proliferation inhibition and enhanced apoptosis, correlating with caspase-3 activation and ROS upregulation. Molecular analysis revealed a profound inhibition of the ubiquitin-proteasome system. MG132 also significantly increased the expression of cisplatin-induced pro-inflammatory cytokines, suggesting a transition from chronic to acute inflammation.</p><p><strong>Conclusion: </strong>MG132 enhances the therapeutic efficacy of cisplatin in human EC cells by suppressing the ubiquitin- proteasome pathway, reducing cell viability, enhancing apoptosis, and shifting the inflammatory response. These findings highlighted the potential of MG132 as an adjuvant in endometrial cancer chemotherapy. Further research is needed to explore detailed mechanisms and clinical applications of this combination therapy.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"281-291"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142360951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}