Effect of L-carnitine on cultured murine melanoma cells exposed to azelaic acid.
The cytotoxic effect of azelaic acid on murine melanoma cells in culture is due, at least in part, to an antimitochondrial action. We investigated the possibility that the addition of carnitine to the medium may increase the transport of azelaic acid into the mitochondria and thereby increase its cytotoxic effect. Using mitochondrial cross-sectional area measured from electron micrographs as a criterion for mitochondrial damage, we found that the addition of L-carnitine to the culture medium had no effect either alone or with a low (10(-3) M) concentration of azelaic acid. At a high concentration (5 X 10(-2) M) azelaic acid caused swelling and disruption of the mitochondria to such an extent that this was not increased by carnitine. At 10(-2) M azelaic acid, however, some swelling of the mitochondria occurred which was significantly increased by the addition of carnitine. This indicates that carnitine-mediated transport of the diacid into the mitochondria had occurred. We conclude that carnitine may reduce the time or concentration needed for azelaic acid to have a toxic effect on the malignant melanocyte.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002331:Carnitine / Q000494:pharmacology*; D002460:Cell Line; D003998:Dicarboxylic Acids / Q000494:pharmacology*; D008545:Melanoma / Q000648:ultrastructure*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000648:ultrastructure
D000970:Antineoplastic Agents; D003998:Dicarboxylic Acids; C010038:azelaic acid; D002331:Carnitine