The Sound of Evolution
Cisplatin
Mechanism of action:
Cisplatin is a platinum-based alkylating-like agent. After entering the cell, cisplatin is exposed to the relatively low intracellular chloride concentration compared with plasma, causing its two chloride ligands to be replaced by water molecules and forming the active species [Pt(NH₃)₂(H₂O)₂]²⁺. This aquated complex is more electrophilic and can react covalently with DNA bases, especially guanine. It causes both intrastrand cross-links and interstrand cross-links in DNA. These lesions prevent DNA replication and transcription, trigger the cellular DNA damage response, and activate apoptotic pathways, often involving p53 and related mechanisms.
Reference(s):
1. Garcia Sar D et al. (2008). In vivo detection of DNA adducts induced by cisplatin using capillary HPLC-ICP-MS and their correlation with genotoxic damage in Drosophila melanogaster. Anal Bioanal Chem.
2. Sharma S et al. (2007). Molecular dynamic simulations of cisplatin- and oxaliplatin-d(GG) intrastand cross-links reveal differences in their conformational dynamics. J Mol Biol.