CYTOTOXICITY OF LIPOIC ACID AND DIHYDROLIPOIC ACID AGAINST MALIGNANT MURINE LEUKEMIA-CELLS - A COMPARISON WITH ASCORBIC-ACID AND DEHYDROASCORBIC ACID

Lipoic acid (LA) is an endogenous thiol which is reduced to dihydrolip oic acid (DHLA) in vivo. Both LA and DHLA act as antioxidants as do as corbic acid (AA) and its oxidative product, dehydroascorbic acid (DHAA ). It has been postulated that LA and DHLA interact directly with pero xy radicals in the cellular membrane and can recycle tocopheroxyl radi cals back into tocopherol by a cascade mechanism involving the reducti on of ascorbate. AA and DHAA have also been shown to have antitumor ac tivity. However, very little is known about the cytotoxicity of DHLA a nd LA. In the present study, we compared the antitumor activity of DHL A and LA on the growth of murine leukaemia P388D1 cell line to AA and DHAA. DHLA was very lethal to the fast growing malignant cells even at a low concentration with ED50 0.4 mu g/ml. In contrast, LA, AA and DH AA were non-toxic at lower concentrations, but toxicity increased with increasing concentrations. LA has an ED,, of 6.0 mu g/ml whereas both AA and DHAA have an ED50 of 3.5 mu g/ml. These results suggest that D HLA is considerably more cytotoxic than AA and DHAA. Med Sci Res 26:46 1-463 (C) 1998 Lippincott-Raven Publishers.