Anti-cancer agents in medicinal chemistry最新文献

{"title":"Quercetin Suppresses Glioma Stem Cells via Activating p16-INK4 Gene Expression through Epigenetic Regulation.","authors":"Jianliang Li, Jingchen Li, Erkun Guo","doi":"10.2174/0118715206332048241126095207","DOIUrl":"https://doi.org/10.2174/0118715206332048241126095207","url":null,"abstract":"<p><strong>Objectives: </strong>Our study aimed to explore the effects of quercetin on glioma stem cells in patients with brain tumors.</p><p><strong>Methods: </strong>Human glioblastoma cell line, U373MG, or glioma stem cell lines, were treated with quercetin. Cell viability was determined by using the cell counting kit 8 assays. Cell apoptosis was determined by using the Annexin-V reagent. Western blotting and qPCR were used to detect the protein and mRNA levels of cyclindependent kinase inhibitor 2A (p16INK4a). Chromatin immunoprecipitation analysis was used to determine the enrichment of H3K27me3 on the p16-INK4 locus with or without quercetin.</p><p><strong>Results: </strong>Treatment with quercetin inhibited cell viability and induced cell apoptosis in U373MG cells. Moreover, treatment with quercetin inhibited the cell viability of four glioma stem cell lines (G3, G10, G15, and G17) from brain tumor samples at high concentrations while having no obvious effects for the other two glioma stem cell lines (G9 and G21). Treatment with quercetin increased the mRNA and protein levels of p16- INK4 in glioma stem cell lines. The study of the underlying mechanism revealed that treatment with quercetin reduced H3K27me3 (an epigenetic modification to the DNA packaging protein histone H3) levels at the p16-INK4 locus.</p><p><strong>Conclusions: </strong>In conclusion, quercetin inhibits glioma cell growth by activating p16-INK4 gene expression through epigenetic regulation.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143121989","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":"Antibody Drug Conjugates (ADCs): Shaping the Future of Precision Oncology.","authors":"Irene Sevilla-Carrillo, Eloína García-Tercero, Carlos Alonso-Moreno, Carmen Moya-Lopez","doi":"10.2174/0118715206348204241128063329","DOIUrl":"https://doi.org/10.2174/0118715206348204241128063329","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) are a groundbreaking advancement in targeted cancer therapy, combining the precision of monoclonal antibodies with the potency of cytotoxic drugs. This review first outlines the components of ADCs and their mechanisms of action before providing a comprehensive overview of the current state of ADC technology. It covers both FDA-approved ADCs and those in various stages of clinical development, as well as future research directions. The review also explores recent innovations, such as bispecific antibodies and pro-body-drug conjugates, which offer promising new strategies for improving efficacy and minimizing off-target effects. The review emphasizes the need for ongoing research to optimize ADC design and develop novel approaches to enhance their therapeutic potential.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143121981","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 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":"https://doi.org/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 in-vitro 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":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-30","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":"Precision Therapy for Prostate Cancer: Advancements in Polymeric Nanocarrier Systems.","authors":"Lalit Kumar, Ritesh Rana, Nusrat K Shaikh, Sumit Kumar, Vikas Aggarwal, Komal Komal, Vuluchala Jyothiraditya","doi":"10.2174/0118715206360906241223120425","DOIUrl":"https://doi.org/10.2174/0118715206360906241223120425","url":null,"abstract":"<p><strong>Introduction: </strong>Prostate cancer is a major worldwide health concern, and existing treatments often face challenges such as drug resistance, systemic toxicity, and insufficient targeting. Polymeric nanocarriers are currently employed as sophisticated tools in the field of oncology, offering the possibility to augment the administration and efficacy of anticancer therapies. In order to effectively eradicate prostate cancer, this review delves into the function of polymeric nanocarriers.</p><p><strong>Methods: </strong>Databases such as PubMed, ScienceDirect, and Google Scholar were utilized to do a comprehensive literature assessment. For this search, we used terms like \"polymeric nanocarriers,\" \"prostate cancer,\" \"drug delivery,\" and \"nanotechnology.\"</p><p><strong>Results: </strong>Studies have shown that polymeric nanocarriers greatly improve the delivery and effectiveness of treatments for prostate cancer. Nanocarriers enhance the solubility, stability, and bioavailability of drugs, resulting in improved therapeutic effects. Functionalization using targeting ligands, such as folic acid and prostate-specific membrane antigen (PSMA) antibodies, has demonstrated the ability to enhance targeted specificity, resulting in a decrease in off-target effects and systemic toxicity. Polymeric nanocarriers facilitate precise and prolonged drug delivery, leading to elevated drug levels in tumor tissues.</p><p><strong>Conclusion: </strong>Polymeric nanocarriers are a notable breakthrough in the management of prostate cancer, providing precise medication administration, decreased toxicity, and improved therapy effectiveness. However, additional study is necessary to enhance the design of nanocarriers, evaluate their long-term safety, and enable their use in clinical applications. Continued interdisciplinary research and collaboration are essential for addressing current obstacles and maximizing the promise of polymeric nanocarriers in the treatment of prostate cancer.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143121987","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":"Cytotoxic Effects Of <i>Lecaniodiscus Cupanioides</i> (Planch.) Extract and Triterpenoids-derived Gold Nanoparticles On MCF-7 Breast Cancer Cell Lines.","authors":"R Magadani, Derek Tantoh Ndinteh, S Roux, Louisiane Patrick Nangah, Item Justin Atangwho, Daniel Ejim Uti, Esther U Alum, Simeon Ikechukwu Egba","doi":"10.2174/0118715206325529241004064307","DOIUrl":"https://doi.org/10.2174/0118715206325529241004064307","url":null,"abstract":"<p><strong>Background: </strong>The prevalent disease known as breast cancer has a significant impact on both men's and women's health and quality of life.</p><p><strong>Aim: </strong>The aim of this study was to explore the potential roles of Lecaniodiscus cupanioides (planch.) extract and triterpenoid-derived gold nanoparticles (AuNPs) in cancer therapy, specifically targeting MCF-7 breast cancer cell lines.</p><p><strong>Methods: </strong>Gold nanoparticles were synthesized utilizing triterpenoid (ZJ-AuNPs) and leaf extract from Lecaniodiscus cupanioides (LC-AuNPs). Fourier transform infrared spectroscopy (FTIR), Dynamic light scattering (DLS), High-resolution transmission electron microscopy (HRTEM), and UV-vis spectroscopy were employed to characterize the nanoparticles. Additionally, the MTT assay was used to assess the impact of AuNPs on cancer cell viability using MCF-7 breast cancer cell lines.</p><p><strong>Results: </strong>Analysis of ZJ-AuNPs and LC-AuNPs revealed DLS zeta potentials of -31.8 and -35.8 mV, respectively, and a corresponding UV-vis absorption maxima at 540 and 550 nm. Also, the ZJ-AuNPs and LC-AuNPs had respective zeta-sizes that ranged from 25.84 to 35.98 nm and polydispersive index values between 0.2360 and 0.773.Furthermore, the presence of the chemical groups -OH and -NH was shown to be necessary for the green method of capping and reducing the gold nanoparticles. Nevertheless, a significant decrease in cell viability percentages was noted in the MTT experiment, accompanied by an increase in the quantity or concentration of the nanoparticles for both ZJ-AuNPs and LC-AuNPs.</p><p><strong>Conclusion: </strong>Given the data obtained in this study, the biosynthesized ZJ-AuNPs and LC-AuNPs were shown to possess potent cytotoxic effects on breast cancer cells. Hence, they may be valuable tools in the development of new cancer chemotherapy drugs.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051395","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":"Adenoviral Therapy for Cervical Cancer: From Targeted Modification to Immunotherapy.","authors":"Yufeng Li, Haibin Zhang, Wenhu Xin, Tiansheng Qin","doi":"10.2174/0118715206338559241112060553","DOIUrl":"https://doi.org/10.2174/0118715206338559241112060553","url":null,"abstract":"<p><p>Cervical cancer is a significant global health threat, ranking as the fourth most common malignancy among women and resulting in over 300,000 deaths annually. Although screening and vaccination initiatives have led to a decline in incidence rates, treatment options for advanced or recurrent cervical cancer remain inadequate, often proving ineffective and costly. In this context, adenoviral therapy has emerged as a promising strategy to enhance therapeutic outcomes. Adenoviruses are non-enveloped viruses that can efficiently infect a wide range of cells, including tumor cells, while exhibiting a favorable safety profile, making them suitable candidates for clinical applications. Adenoviral vectors possess the unique ability to package large segments of therapeutic genes, allowing for diverse treatment approaches, including oncolytic virotherapy, which selectively targets and destroys tumor cells while stimulating robust immune responses. By engineering adenoviruses to express tumor suppressor genes such as p53, researchers can restore critical apoptotic pathways often disrupted in cervical cancer. Furthermore, genetic modifications to capsid proteins can enhance the targeting of tumor cells and reduce the immunogenicity associated with these viral vectors. Additionally, adenoviral vectors can serve as delivery systems for therapeutic vaccines against HPV oncogenes E6 and E7, promoting effective immune responses and potentially preventing disease progression. The combination of adenoviral therapy with immune checkpoint inhibitors offers a novel approach to overcoming the immunosuppressive tumor microenvironment, enhancing overall antitumor immunity. Overall, this review highlights the significant advancements in adenoviral therapy for cervical cancer, emphasizing the need for further research to optimize these strategies and translate preclinical successes into effective clinical applications. By harnessing the full potential of adenoviral vectors, we can improve treatment options for patients who have cervical cancer, paving the way for more personalized and effective therapeutic interventions.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051394","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":"Harnessing Therapeutic Potential of Allicin Against Cancer: An Exploratory Review.","authors":"Anmol Saini, Vishakha Saini, Geeta Deswal, Bhawna Chopra, Ajmer Singh Grewal, Ashwani K Dhingra","doi":"10.2174/0118715206343978241223080625","DOIUrl":"https://doi.org/10.2174/0118715206343978241223080625","url":null,"abstract":"<p><strong>Background: </strong>The biological name of garlic is Allium sativum L., a familiar spice with various health benefits. These benefits are mainly attributable to the compound diversity of garlic, which includes saponins, polysaccharides, organic sulfides, and phenolic compounds. Allicin exhibits therapeutic activity such as antibacterial, anticancer, anti-inflammatory, immunomodulatory, anti-diabetic, and cardiovascular protection. This present study explores the anticancer potential of allicin, including cell line studies that examine its effects on various cancer types by analyzing the growth inhibition of cancer cells at different allicin concentrations.</p><p><strong>Aim: </strong>This study aims to present a concise overview of allicin, update patent statistics, and provide detailed insights into its wide range of therapeutic benefits, with a particular emphasis on its anticancer properties.</p><p><strong>Methods: </strong>A literature review has been conducted using reliable sources, including ClinicalTrials.gov, ScienceDirect, PubMed, Scopus, and other reputable foundations, to assess the true potential of allicin in cancer therapeutics.</p><p><strong>Results: </strong>Allicin, a naturally occurring compound in garlic, represents a promising treatme nt approach for cancer due to its potent anticancer properties. Cell line studies have shown that various concentrations of allicin significantly inhibit cancer cell growth, underscoring its effectiveness against cancer types such as breast, pancreatic, liver, renal, osteosarcoma, gastric, colorectal, and stomach cancers. By effectively targeting cancer cells, allicin stands out as a potential therapeutic agent.</p><p><strong>Conclusion: </strong>The primary goal of the review is to highlight the anticancer potential of allicin, along with an overview of clinical and patent studies.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031847","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":"Cyclic Lipopeptides as Selective Anticancer Agents: In vitro Efficacy on B16F10 Mouse Melanoma Cells.","authors":"Ali N Hmedat, Micjel C Morejon, Daniel G Rivera, Nebojsa Đ Pantelic, Ludger A Wessjohann, Goran N Kaluderovic","doi":"10.2174/0118715206351208250102114944","DOIUrl":"https://doi.org/10.2174/0118715206351208250102114944","url":null,"abstract":"<p><strong>Objective: </strong>In this study, 25 synthetic cyclic lipopeptides (CLPs) were investigated for their anticancer potential against mouse melanoma (B16F10) cells, human prostate cancer (PC-3), human colorectal adenocarcinoma (HT-29) and mouse embryonic fibroblast (NIH3T3) cells.</p><p><strong>Methods: </strong>The cytotoxic activity of investigated compounds was evaluated using MTT and CV assays. In order to examine the mechanism of action of the most potent compound cell cycle analysis, apoptosis assay, caspase activity, CFSE and DHR staining, DAF-FM, autophagy and immunocytochemistry caspase-3 assays were performed.</p><p><strong>Results: </strong>During the fast screening, compound 9, was identified as prospective active CLP against B16F10 cell line at 10 μM concentration. MTT and CV assays exhibited at least four times higher cytotoxic potential of 9 (IC50 = 8.4±1.3 μM, MTT; 10.6±1.1 μM, CV) in comparison to control drug natural occurring CLP surfactin (IC50 = 50.3±0.6 μM, MTT; 40.4±0.3 μM, CV). The use of flow cytometry analysis confirmed that apoptosis was involved in the death of B16F10 cells after treatment with 9, as demonstrated also by DAPI staining. Caspase activity could be detected during cell death (ApoStat assay, immunocytochemistry caspase-3 assay). Compound 9 provokes enhancement of nitric oxide (NO) production in B16F10 cells but does not trigger ROS/RNS generation or autophagy.</p><p><strong>Conclusion: </strong>The study highlights synthetic compound 9 superior tumor-specificity and potential as an anticancer agent compared to surfactin and cisplatin. These findings could guide the development of more selective and less harmful macrocyclic lipopeptides for cancer therapy.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031843","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":"Potentials of N-Acyl hydrazones Against Colorectal Cancer: A Mini Review.","authors":"Darna Mounika, Sai Satya Sri Pulla, Swapnil Anil Sule, Vidya Jyothi Alli, Surender Singh Jadav","doi":"10.2174/0118715206356253241223040825","DOIUrl":"https://doi.org/10.2174/0118715206356253241223040825","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a malignant gastrointestinal tract disorder with high occurrence and mortality index and showing an upsurge. Standard therapies for treating CRC are surgery and chemotherapy. Despite great effort in developing effective treatments, the progress is limited due to its relapse and recurrence. Prognosis of metastatic CRC is always complicated. This condition can be evaded by a novel approach i.e., targeted therapy which increases the survival rate in CRC patients by blocking important pathways and acting on immune checkpoints. Drugs with N-acyl hydrazones (NAH) are currently being employed treatment of infectious diseases and disorders. NAH in combination with diverse heterocycles, natural product isolates are identified as interesting CRC inhibitors under-explored. This review provides an overview of the existing CRC targeted compounds having acyl hydrazones, hydrazine, hydrazides moieties, and their underlying mechanisms towards different CRC cell lines, together with a discussion of their limitations and future trends.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031851","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 Potential of S4 on Non-small Cell Lung Cancer Cells: Impact on Proliferation, Apoptosis, Senescence, and Metabolome Profile.","authors":"Turan Demircan, Mervenur Yavuz, Aydın Bölük","doi":"10.2174/0118715206350735241224073200","DOIUrl":"https://doi.org/10.2174/0118715206350735241224073200","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer is a highly aggressive tumor with limited therapeutic options. The misregulation of Androgen Receptor (AR) signaling has been observed in lung cancer. Therefore, inhibiting AR signaling is a promising strategy for treating lung cancer.</p><p><strong>Objective: </strong>Selective Androgen Receptor Modulators (SARMs) are small molecule drugs with a high affinity for the AR. S4, a member of SARMs was potentially positioned as a promising therapeutic agent in A549 lung cancer cells owing to its high bioavailability, lesser side effects, and novelty in cancer.</p><p><strong>Methods: </strong>We employed several techniques to investigate the potential anti-carcinogenic effect of S4 on A549 cells at cellular level. The cytotoxicity of S4 was investigated thorough MTT, and the IC50 value was identified as 0.22 mM. Then, the anchorage-dependent and -independent colonization of cells were assessed by colony formation and soft agar assays, respectively. Additionally, migration capacity, apoptosis, proliferation, senescene, cell-cycle progression of cells was examined thoroughly. In addition, gene expression profile and metabolome signature were explored via qRT-PCR and metabolomics, respectively to provide molecular links for S4 mode of action.</p><p><strong>Results: </strong>Our findings demonstrate that S4 inhibited growth, migration, and proliferation while inducing apoptosis. S4 significantly upregulated the BAX, CDKN1A, PUMA, and GADD45A genes while downregulating MKI67, BIRC5, and PCNA expression. S4 treatment drastically altered the metabolome signature, and enrichment of cancer related pathways by altered metabolites was noteworthy.</p><p><strong>Conclusion: </strong>We report the first study evaluating the potential anti-carcinogenic effects of S4 on lung cancer invitro which would bridge the gap on the utility of SARMs as inhibitors of lung cancer. Our results suggest that S4 could be considered as a promising drug candidate to test further for lung cancer treatment.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021761","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}