The effects of calcium antagonists on anthrone skin tumor promotion and promoter-related effects in SENCAR mice

The present study investigated a possible role for Ca2+ in skin tumor promotion by anthrones. This was accomplished by testing the effects of two Ca2+ antagonists, verapamil and 3,4,5-trimethoxybenzoic acid 8-(diethylamino) octyl ester (TMB-8), on tumor promotion and promoter-related effects induced by the anthrone chrysarobin in SENCAR mice. Verapamil and TMB-8 both effectively inhibited epidermal ornithine decarboxylase (ODC) induction by a single application of chrysarobin. Both Ca2+ antagonists inhibited anthrone-induced skin edema and epidermal hyperplasia. Additionally, both verapamil and TMB-8 slightly inhibited (20–21% at the highest doses) tumor promotion with chrysarobin. Although the inhibition by both Ca2+ antagonists was not statistically significant (P>0.05) in either case, the fact that both compounds produced a similar inhibition suggests that this effect may be biologically relevant. Collectively, the data suggest a possible role for Ca2+ in the process of skin tumor promotion by anthrones.