Inhibition of transcription by platinum antitumor compounds

作者：Ryan C. Todd, Stephen J. Lippard · 发表于：Metallomics · 年份：2009 · DOI：10.1039/b907567d · 被引用次数：539 · 研究领域：Metal complexes synthesis and properties、DNA and Nucleic Acid Chemistry、Ferrocene Chemistry and Applications

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. Platinum anticancer compounds bind to nuclear DNA, inhibit transcription, and induce apoptosis. Insight into the molecular mechanism of this process will aid researchers in the design of new metal-based chemotherapeutic agents.