Activity of platinum drugs against melanoma cell lines: is it modulated in vitro in the presence of tamoxifen?

Cisplatin and carboplatin have been used against human malignant melanoma as single agents and in combination. Tamoxifen is used in the treatment of breast cancer, but has no significant activity against human malignant melanoma. Tamoxifen, however, has been promoted as a modulator in some drug regimens. The addition of tamoxifen to cisplatin or carboplatin has been reported to enhance their activity against the human melanoma cell line T-289. We investigated whether tamoxifen potentiates, in vitro, the activity of cisplatin and carboplatin against C32, G361 and StMl11a melanoma cell lines. Tamoxifen alone at clinically achievable concentrations of 0.1 and 1.0 microM (168 hrs exposure) had no significant effect on growth. No chemopotentiation of the activity of cisplatin or carboplatin was observed with the addition of tamoxifen (0.1 and 1.0 microM). The platinum drugs were added for 1 hr (serially diluted from 100.0 microM). Against the G361 line there was a trend towards chemopotentiation of cisplatin by 0.1 microM of tamoxifen. However, this did not reach statistical significance. Tamoxifen (5.0 and 10.0 microM) produced some inhibitory activity, and a trend towards synergy with cisplatin was observed. However, these concentrations are not clinically feasible. Previous reports detecting synergistic interaction between tamoxifen (0.1 and 1.0 microM), and the platinum compounds against the T-289 melanoma cell line cannot be supported in our in vitro system.