title: Biomolecular targets for platinum antitumor drugs.
abstract: Cis-diamminedichloroplatinum(II) (cisplatin) is widely used for the treatment of testicular, ovarian, and other forms of cancer. Several second generation platinum centered antitumor drugs have been approved or undergoing phase-3 clinical trial. Cisplatin arrests the cell cycle at the G2 phase by a mechanism commonly known as apoptosis. At the molecular level, it is generally believed that the anticancer properties of these compounds are due to the covalent binding to DNA. In addition to DNA binding, the platinum drugs bind and interact with proteins and enzymes. The toxic effects of the drugs have been usually attributed to protein binding. However, a growing body of work points to much more complex anticancer mechanisms involving direct and indirect interactions of platinum compounds with proteins and enzymes. In this review, a discussion on the strength and weaknesses of DNA binding mechanism followed by enzymes and protein interactions with the drugs are presented for the comprehensive understanding of apoptosis. The purpose of this review is to encourage researchers to explore metallobiochemistry of platinum drugs focusing attention to cellular and molecular events beyond DNA binding.
authors.affiliation: Department of Chemistry, Kent State University, Kent, OH 44242, USA. rbose@kent.edu
authors.forename: Rathindra N
authors.initials: RN
authors.lastname: Bose
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000187:drug effects; D005978:Glutathione / Q000737:chemistry; D006801:Humans; D019384:Nucleic Acid Synthesis Inhibitors; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D019384:Nucleic Acid Synthesis Inhibitors; D009944:Organoplatinum Compounds; D014157:Transcription Factors; D005978:Glutathione; D002945:Cisplatin