Effect of Dicarboxylic Acids on Harding-Passey and Cloudman S91 Melanoma Cells in Tissue Culture

Abstract

Clinically, dicarboxylic acids have a cytotoxic effect on the abnormally hyperactive and malignant epidermal melanocyte, and diacids from C8 to C13 have been shown to inhibit mitochondrial oxidoreductases. Here, their effect on the growth kinetics and ultrastructure of murine melanoma cells in culture is examined. Cultures of Harding-Passey and Cloudman S91 melanoma cells were exposed to single doses of the disodium salts of C12, C9, and C6 (which does not significantly inhibit mitochondrial enzymes) dicarboxylic acids at concentrations of 10(-3) M to 10(-1) M. With C12 and C9, viability and cell proliferation over 3 days were significantly affected by concentrations greater than 10(-2) M. With exposure to C6 at 10(-1) M and to medium to which NaCl was added to produce equal osmolarity, the effect was much less. Electron microscopy of cells exposed to C9 at 10(-1) M for 1 h and 6 h revealed massive swelling of mitochondria with destruction of cristae, but plasma and nuclear membranes and membranes of endoplasmic reticulum were intact. Similar damage was not seen with C6 at 10(-1) M nor with equiosomolar NaCl. The results confirm (1) the cytotoxicity of dicarboxylic acids for malignant melanocytes, and (2) that the mitochondrion is a prime target for their action.