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PMID: 20046924 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Inhibition of transcription by platinum antitumor compounds.

Metallomics : integrated biometal science ·Vol. 1 ·No. 4 ·2009-00-00 ·Pages 280-91

Todd RC, Lippard SJ

Abstract

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.

MeSH Terms
Antineoplastic Agents/pharmacology Humans Organoplatinum Compounds/pharmacology Transcription, Genetic/drug effects
Chemicals
Antineoplastic Agents Organoplatinum Compounds
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Todd Ryan C
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Lippard Stephen J
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Article Info
Journal
Metallomics : integrated biometal science
Abbr.
Metallomics
ISSN
1756-591X
DOI
10.1039/b907567d
Published
2009-00-00
Pages
280-91
Language
English
Region
England
NLM ID
101478346
PMCID
PMC2752884
Subset
IM
Grants
NCI NIH HHS · R01 CA034992 · United States
NCI NIH HHS · R37 CA034992 · United States
NCI NIH HHS · R37 CA034992-26 · United States
NCI NIH HHS · CA034992 · United States
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PubMed source DOI: 10.1039/b907567d PMC Full Text View journal details
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