Chemopreventive effects of stevioside against naturally occurring tumor promoter, Teleocidin
In our continuous search for chemopreventive active constituents from natural sources, the natural sweetener stevioside have been screened using the in vitro synergistic assay indicated by inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by TPA. In this assay, stevioside and related compounds exhibited potential inhibitory effects on EBV-EA activation without cytotoxicity on Raji cells. In our experiments, the inhibitory effects of stevioside, steviol and isosteviol were greater than that of glycyrrhizin, which is a known anti-tumour promoting agent. On the basis of the results of this in vitro assay, the inhibitory effects of these compounds were investigated in a two-stage carcinogenesis test of mouse skin tumour using DMBA as an initiator and teleocidin as a another type potential promoter. Teleocidin isolated from Streptomyces mediocidicus also exerts a broad spectrum of biological effects in addition to tumour promoting activity in vivo with potencies equivalent to those of TPA. In the present work, stevioside was topically administred for 1h before each promotion treatment, using teleocidin and inhibited mouse skin caricinogenesis promoted by indole alkaloids type compounds. These effects were essentially identical with those produced by TPA  and we thought that stevioside also might be as potential as TPA in term of anti-tumour-promoting activity on mouse skin against teleocidin. This is the first finding to prove that stevioside may protect tumour promoting potency from microbiological products.
Acknowledgements: Teleocidin was provided by Prof. K. Irie, Kyoto University.
Reference: 1. Konoshima, T. et al. (2002) Pure. Appl. Chem. 74:1309.