The cytotoxic action of four ammine/amine platinum(IV) dicarboxylates: a flow cytometric study

British Journal of Cancer
M G OrmerodK R Harrap

Abstract

We have used flow cytometry to study the mechanism of cytotoxic action of a series of ammine/amine Pt(IV) dicarboxylates [ammine diacetatodichloro(cyclohexylamine) platinum(IV), JM216; ammine dibutyratodichloro(cyclohexylamine)platinum(IV), JM221; ammine diacetatodichloro(propylamine)platinum(IV), JM223; ammine dibenzoatodichloro(propylamine)platinum(IV), JM244]. JM216 has been shown to have clinical potential and has recently entered phase II trials. All the compounds caused a slowdown in S-phase transit followed by a block in G2. Cells died either through apoptosis (largely during S-phase) or by failing to overcome the G2 block (some days after treatment). In G2, the cells either divided or enlarged and died. At equitoxic doses, JM216 showed the most apoptotic cells and had the most platinum bound to the DNA; JM244 showed the fewest apoptotic cells and had the least platinum bound to DNA. We suggest that whether apoptosis was triggered or not was governed by the total amount of Pt bound to the DNA; the type of lesion was more important in determining whether a cell became blocked in G2.

Citations

Jan 10, 2002·Redox Report : Communications in Free Radical Research·M G Ormerod
Sep 19, 2000·Antimicrobial Agents and Chemotherapy·T WatanabeT Matsumoto
May 22, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alejandro D RicartKyriakos P Papadopoulos

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis