title: Chemotherapy-induced apoptosis in melanoma cells is p53 dependent.
abstract: Metastatic melanomas are often resistant to chemotherapy. To study whether the p53 mutational status affects chemosensitivity, we compared the responses to chemotherapy of four melanoma cell lines containing the wild-type p53 and four cell lines carrying the mutant p53. Cisplatin, at 10 microM, virtually killed all the cells in the wild-type p53 cell lines, while 57-95% of the cells in the mutant p53 cell lines survived (P = 0.005). After treatment with 100 nM of vincristine, on average 18% of the wild-type p53 melanoma cells survived compared with 55% of the mutant p53 cells (P = 0.04). After treatment with 40 nM, 200 nM or 1 microM of camptothecin the survival rates were, on average, 16%, 8% and 4% for the wild-type p53 melanoma cells, compared with 89%, 67% and 38% for the mutant p53 cells, respectively (P = 0.00004, P = 0.003 and P = 0.04, respectively). The anticancer agents were not toxic to normal melanocytes at doses inducing cytotoxicity in wild-type p53 melanoma cells. The main mechanism of cytotoxicity appears to be drug-induced apoptosis. Cisplatin, camptothecin and vincristine all induced apoptosis in wild-type p53 melanoma cells, but not in mutant p53 cells. Our results suggest that chemotherapy-induced apoptosis in melanoma cells is p53 dependent, and mutation of the p53 gene is an indicator of drug resistance in melanoma.
authors.affiliation: Department of Medicine, University of British Columbia and the Vancouver Hospital and Health Science Centre, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Li
authors.forename: L
authors.initials: L
authors.lastname: Tang
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.forename: V
authors.initials: V
authors.lastname: Tron
authors.forename: V
authors.initials: V
authors.lastname: Ho
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002166:Camptothecin / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000032:analysis; D004587:Electrophoresis, Agar Gel; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008544:Melanocytes / Q000187:drug effects; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D009154:Mutation; D012878:Skin Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D014750:Vincristine; D002945:Cisplatin; D002166:Camptothecin