Cytotoxicity of etretinate and vindesine

The effects of an aromatic retinoid, etretinate and a vinca alkaloid, vindesine were investigated by culture of malignant melanoma cells in vitro with these two agents; either separately or in combination. Etretinate inhibited growth of a murine melanoma but only minimal effects were recorded with two human melanomas. Vindesine however, was inhibitory for all of the cell lines and this effect was enhanced in the presence of the retinoid. Entry of 3H labelled vindesine or etretinate into drug free cells was followed in the absence or presence of unlabelled drug. It was found that etretinate enhanced cellular uptake of vindesine in two of the cell lines and this may be responsible for the enhanced toxicity of vindesine in the presence of etretinate. The human melanoma which did not exhibit retinoid stimulated vindesine uptake, appeared to be intrinsically sensitive to the vinca alkaloid. No effect on cellular retinoid uptake by vindesine was recorded in any of the melanomas. The results indicate that the intracellular concentrations combined with the intrinsic sensitivities of each cell line to etretinate and vindesine determines the toxic response.