safranine-t and Melanoma

Despite having lower cell membrane potentials, four human melanoma cell lines and HeLa cells accumulated the membrane probe triphenylmethylphosphonium ion (TPMP, 2 microM) 2-10 fold more rapidly than human fibroblasts, and did not reach equilibrium during the 2 h incubation period studied. The difference was not due to drug toxicity, although at much higher levels of TPMP (greater than 20 microM) selective killing of melanoma cells compared with fibroblasts was observed. Some dependence of TPMP accumulation upon membrane potential was indicated by inhibition of uptake in fibroblasts depolarised by culture in calcium-deficient medium. Melanoma cells exhibited no change in TPMP uptake or membrane potential under these conditions. Uptake of safranine, an indicator of mitochondrial membrane potential, did not follow the TPMP pattern. Thus, the anomalous accumulation of TPMP by human tumour cells appeared to result from either carrier-mediated transport or rapid intracellular metabolism and could not be used to determine cell membrane potentials.

Topics: Cell Survival; Cell Transformation, Neoplastic; Fibroblasts; Humans; Kinetics; Melanoma; Membrane Potentials; Onium Compounds; Phenazines; Trityl Compounds