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. Oxaliplatin, L-OHP, is a third-generation platinum antitumour analogue in which the 1, 2-diaminocyclohexane (DACH) ligand substitutes for the amino groups of cisplatin (1). Oxaliplatin, in combination with 5-Fluorouracil (5-FU) and folinic acid (FA) is indicated as first-line therapy for metastatic colorectal cancer (2). It is given at the recommended doses of 130 mg/m 2 q3 weeks or 85 mg/m 2 q2 weeks, as a 2- to 6-h intravenous infusion (3). Studies carried out in cell lines of the NCI anticancer drug screening panel comparing oxaliplatin and other Pt agents have shown that cisplatin and oxaliplatin have different sensitivity profiles, suggesting that the two complexes may have different mechanism(s) of action and/ or resistance (4). In general, the cytotoxicity of platinum compounds in cancer cells can be related to the inhibition of DNA synthesis or to saturation of the cellular capacity to repair Pt-DNA. The cytotoxic activity of L-OHP is initiated by the formation of DNA adducts. L-OHP causes more DNA strand-breaks compared to cisplatin (5). DACH- platinum adducts formed by L-OHP are more bulky and more hydrophobic than platinum adducts formed by cisplatin and carboplatin. As a result, the DACH- platinum adducts are more effective in inhibiting DNA synthesis (6).