Cell cycle arrest by oxaliplatin on cancer cells.

Oxaliplatin (L-OHP) is the only platinum compound to show activity in colorectal cancer. We evaluated the cytotoxicity of L-OHP on four human cancer cell lines and its influence on the cell cycle, when treated during long exposure (72 h) and different post-incubation times (24 or 72 h). We used a panel of cell lines: HT29 (colon cancer), MCF7 (breast cancer), Hela (uterine cervix) and A549 (lung adenocarcinoma). Inhibition concentration (IC)(50) was assessed by MTT assay. Cell cycle modifications were determined using dual parameter bromodeoxyuridine and propidium iodide. L-OHP yielded a superior cytotoxicity on HT29 and MCF7 relative to Hela and A549 after treatment, the post-incubations demonstrate that growth inhibition was irreversible for HT29 and Hela cell lines contrary to MCF7 and A549. The main effects of L-OHP are G2/M cell cycle arrest and transient S phase delay. Taken together, L-OHP treatment results on HT29, MCF7 and Hela, are in favor of lengthening the infusion duration to patients during further clinical trials.

Cell cycle arrest and apoptosis induced by oxaliplatin (L-OHP) on four human cancer cell lines.

BACKGROUND: The effects of oxaliplatin (L-OHP) on cell cycle and apoptosis were examined. MATERIALS AND METHODS: The HT29, MCF7, Hela and A549 cell lines were treated and dual parameter flow cytometry BrdU/PI was then performed to monitor cell cycle modifications. Annexin V-FITC and PI probes were used for the detection of apoptosis. RESULTS: The cells were treated for 3 h followed or not by 24 and 72 h of post-incubation. No changes were observed after 3 h of treatment, while after 24 h of post-incubation, all the cells except A549 were predominantly accumulated in the G2/M-phase; this accumulation was time-dependent. Apoptosis induction was late and moderate and was observed only after 12 h of treatment and 24 h of post-incubation. CONCLUSION: L-OHP induced cell cycle arrest and moderate apoptosis; these two activities were time-dependent. These findings warrant further investigation into the potential antitumour activity of L-OHP in MCF7 and Hela cells and in lengthening the infusion duration in order to achieve the acquired cellular modifications.