Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Metallomics. 2009;1(4):280-91. doi: 10.1039/b907567d.
Cisplatin, carboplatin, and oxaliplatin are three FDA-approved members of the platinum anticancer drug family. These compounds induce apoptosis in tumor cells by binding to nuclear DNA, forming a variety of structural adducts and triggering cellular responses, one of which is the inhibition of transcription. In this report we present (i) a detailed review of the structural investigations of various Pt-DNA adducts and the effects of these lesions on global DNA geometry; (ii) research detailing inhibition of cellular transcription by Pt-DNA adducts; and (iii) a mechanistic analysis of how DNA structural distortions induced by platinum damage may inhibit RNA synthesis in vivo. A thorough understanding of the molecular mechanism of action of platinum antitumor agents will aid in the development of new compounds in the family.
顺铂、卡铂和奥沙利铂是美国食品药品监督管理局批准的三种铂类抗癌药物。这些化合物通过与核 DNA 结合，形成多种结构加合物，并引发细胞反应，从而诱导肿瘤细胞凋亡，其中之一是抑制转录。在本报告中，我们介绍了（i）对各种 Pt-DNA 加合物的结构研究以及这些损伤对全球 DNA 几何形状的影响的详细回顾；（ii）详细研究了 Pt-DNA 加合物对细胞转录的抑制作用；以及（iii）对由铂损伤诱导的 DNA 结构扭曲如何抑制体内 RNA 合成的机制分析。深入了解铂类抗肿瘤药物的作用机制将有助于该家族新化合物的开发。
