Inhibition of transcription by platinum antitumor compounds.
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.
Todd
Ryan C
RC
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Lippard
Stephen J
SJ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D006801:Humans; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds