Chemotherapy-induced apoptosis in melanoma cells is p53 dependent

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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,µM, virtually killed all the cells in the wildtype 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 wildtype p53 melanoma cells survived compared with 55% of the mutant p53 cells (P=0.04). After treatment with 40 nM, 200 nM or 1 µM 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. © 1998 Rapid Science Ltd

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