Growth inhibition and apoptosis induction of human melanoma cells by ??-hydroxy fatty acids

Abstract

We examined the anti-tumor activity and structure-activity requirements of omega-hydroxy fatty acids (omega-HFAs) on the human melanoma cell line G361. The omega-hydroxystearic acid (omega-HSA) had strong growth-inhibiting and cytotoxic activity. Although omega-hydroxypalmitic acid (omega-HPA) also had growth-inhibiting and cytotoxic activity, these effects were relatively low. The effects of both these acids were dose and time dependent. Further, DNA laddering, which is an index of apoptosis, was also observed in G361 cells on treatment with these compounds. On the other hand, the omega-HFAs tested in this study, omega-hydroxymyristic acid and omega-hydroxyeicosanoic acid, had no growth-inhibiting or cytotoxic activity. Treatment for 12 h with 100 microM of omega-HPA and omega-HSA resulted in the expression of caspase-3 activity, and then increased upon 24 h, suggesting that the cell death induced by omega-HPA and omega-HSA was apoptosis. Fatty acids and dicarboxylic acids, which are analogs of omega-HFAs, had no cytotoxicity. However, fatty alcohols and diols, which have a 16- to 18-carbon chain length had weak cytotoxicity. From these results, the most effective carbon chain length is 18. Furthermore, the hydroxyl group at one end of the carbon chain and the carboxyl group at the other end seem to be required for the cytotoxic effect. At least one end of the carbon chain must have a hydroxyl group. The carbon chain length of omega-HFAs appears to be closely related to the cytotoxicity. This study revealed the potent cytotoxic actions of omega-HFAs on the human melanoma cell line G361.