David Justin M, Rajasekaran Ayyappan K
Department of Biological Sciences, University of Delaware, Newark, DE, USA; Therapy Architects, LLC, Wilmington, DE, USA.
J Kidney Cancer VHL. 2015 Jan 18;2(1):15-24. doi: 10.15586/jkcvhl.2015.21. eCollection 2015.
Gramicidin A (GA) is a channel-forming ionophore that renders biological membranes permeable to specific cations which disrupts cellular ionic homeostasis. It is a well-known antibiotic, however it's potential as a therapeutic agent for cancer has not been widely evaluated. In two recently published studies, we showed that GA treatment is toxic to cell lines and tumor xenografts derived from renal cell carcinoma (RCC), a devastating disease that is highly resistant to conventional therapy. GA was found to possess the qualities of both a cytotoxic drug and a targeted angiogenesis inhibitor, and this combination significantly compromised RCC growth in vitro and in vivo. In this review, we summarize our recent research on GA, discuss the possible mechanisms whereby it exerts its anti-tumor effects, and share our perspectives on the future opportunities and challenges to the use of GA as a new anticancer agent.
短杆菌肽A（GA）是一种形成通道的离子载体，可使生物膜对特定阳离子具有通透性，从而破坏细胞离子稳态。它是一种著名的抗生素，然而其作为癌症治疗药物的潜力尚未得到广泛评估。在最近发表的两项研究中，我们表明GA处理对源自肾细胞癌（RCC）的细胞系和肿瘤异种移植具有毒性，肾细胞癌是一种对传统疗法高度耐药的毁灭性疾病。发现GA兼具细胞毒性药物和靶向血管生成抑制剂的特性，这种组合在体外和体内均显著抑制了RCC的生长。在本综述中，我们总结了我们最近对GA的研究，讨论了其发挥抗肿瘤作用的可能机制，并分享了我们对将GA用作新型抗癌药物的未来机遇和挑战的看法。
