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.
William-Faltaos
Sara
S
Pharmacology Department, Faculty of Medicine, Pitie-Salpetriere Hospital, 91 Boulevard de l'Hôpital, Door: 417-418, 75634 Paris Cedex 13, France. sara@chups.jussieu.fr
Rouillard
Dany
D
Lechat
Philippe
P
Bastian
Gérard
G
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001973:Bromodeoxyuridine; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007262:Infusions, Intravenous; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D000077150:Oxaliplatin; D011419:Propidium
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D011419:Propidium; D001973:Bromodeoxyuridine