{"title":"An anti-neoplastic tale of metformin through its transport","authors":"","doi":"10.1016/j.lfs.2024.123060","DOIUrl":null,"url":null,"abstract":"<div><p>Metformin is an attractive candidate drug among all the repurposed drugs for cancer. Extensive preclinical and clinical research has evaluated its efficacy in cancer therapy, revealing a mixed outcome in clinical settings. To fully exploit metformin's therapeutic potential, understanding cellular factors relevant to its transport and accumulation in cancer cells needs to be understood. This review highlights the relevance of metformin transporter status towards its anti-cancer potential. Metformin transporters are regulated at pre-transcriptional, transcriptional, and post-translational levels. Moreover, the tumour microenvironment can also influence metformin accumulation in cancer cells. Also, Metformin treatment can regulate its transporters by altering global DNA methylation, protein acetylation, and transcription factors. Importantly, metformin transporters not only influence chemotherapeutic drug toxicity but are also associated with the prognosis and survival of individuals having cancer. Strategic decisions based on the expression and regulation of metformin transporters holds promise for its therapeutic implications and relevance.</p></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2000,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Life sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0024320524006507","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Metformin is an attractive candidate drug among all the repurposed drugs for cancer. Extensive preclinical and clinical research has evaluated its efficacy in cancer therapy, revealing a mixed outcome in clinical settings. To fully exploit metformin's therapeutic potential, understanding cellular factors relevant to its transport and accumulation in cancer cells needs to be understood. This review highlights the relevance of metformin transporter status towards its anti-cancer potential. Metformin transporters are regulated at pre-transcriptional, transcriptional, and post-translational levels. Moreover, the tumour microenvironment can also influence metformin accumulation in cancer cells. Also, Metformin treatment can regulate its transporters by altering global DNA methylation, protein acetylation, and transcription factors. Importantly, metformin transporters not only influence chemotherapeutic drug toxicity but are also associated with the prognosis and survival of individuals having cancer. Strategic decisions based on the expression and regulation of metformin transporters holds promise for its therapeutic implications and relevance.
二甲双胍是所有癌症再治疗药物中颇具吸引力的候选药物。广泛的临床前和临床研究评估了二甲双胍在癌症治疗中的疗效,结果显示临床治疗效果参差不齐。要充分挖掘二甲双胍的治疗潜力,就必须了解与二甲双胍在癌细胞中的转运和蓄积有关的细胞因素。本综述强调了二甲双胍转运体状态与其抗癌潜力的相关性。二甲双胍转运体受转录前、转录和翻译后水平的调控。此外,肿瘤微环境也会影响二甲双胍在癌细胞中的积累。此外,二甲双胍治疗可通过改变全局 DNA 甲基化、蛋白质乙酰化和转录因子来调节其转运体。重要的是,二甲双胍转运体不仅影响化疗药物的毒性,还与癌症患者的预后和存活率有关。基于二甲双胍转运体的表达和调控而做出的战略决策具有治疗意义和相关性。
期刊介绍:
Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed.
The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.