Avicins, a family of triterpenoid saponins from Acacia victoriae (Bentham), suppress H-ras mutations and aneuploidy in a murine skin carcinogenesis model

We tested the ability of avicins, a family of triterpenoid saponins obtaine d from Acacia victoriae (Bentham) (Leguminosae: Mimosoideae), to inhibit ch emically induced mouse skin carcinogenesis. Varying doses of avicins were a pplied to shaved dorsal skin of SENCAR mice 15 min before application of 10 0 nmol of 7,12-dimethylbenz[a]anthracene (DMBA) twice a week for 4 weeks (c omplete carcinogenesis model). The dorsal skin of a second group of mice wa s treated with one dose of 10 nmol of DMBA. Avicins were then applied 15 mi n before repetitive doses off 2 mug of phorbol 12-tetradecanoate 13-acetate (TPA) twice a week for 8 weeks (initiation/promotion model). At 12 weeks, avicins produced a 70% decrease in the number of mice with papillomas and a greater than 90% reduction in the number of papillomas per mouse in both p rotocols. We also observed a 62% and 74% reduction by avicins in H-ras muta tions at codon 61 in the DMBA and DMBA/TPA models, respectively, as well as a significant inhibition of the modified DNA base formation (8-OH-dG) in b oth protocols. Marked suppression of aneuploidy occurred with treatment at 16 weeks in the initiation/promotion experiment. These findings, when combi ned with the proapoptotic property of these compounds and their ability to inhibit hydrogen peroxide (H2O2) generation, nuclear factor-kappaB (NF-kapp aB) activation, and inducible nitric oxide synthase (iNOS) induction report ed elsewhere, suggest that avicins could prove exciting in reducing oxidati ve and nitrosative stress and thereby suppressing the development of human skin cancer and other epithelial malignancies.