Teleocidin from Streptomyces is a potent promoter of mouse skin carcinogenesis

Abstract

Teleocidin, isolated from Streptomyces mediocidicus ISP 5021, is an indole alkaloid. The teleocidin used was composed of teleocidin A, teleocidin B and their isomers. A hydrogenated derivative of teleocidin B, dihydroteleocidin B, was recently reported to have tumor promoting activity in vivo and various biological activities in vitro, with a specific activity comparable to that of 12-O-tetradecanoylphorbol-13-acetate (TPA). This paper describes the potent tumor promoting activity of the parent compound of dihydroteleocidins, teleocidin, on mouse skin in two-stage carcinogenesis. The tumor promoting activity was evaluated by measuring the incidence and yield of tumors, and by histological examination. Groups of mice were given a single application of 100 micrograms of 7,12-dimethylbenz[a]anthracene (DMBA) and then 2.5 micrograms of teleocidin twice weekly or the same dose of DMBA plus 2.5 micrograms of TPA twice weekly. Both groups showed 100% tumor incidence after 24 weeks, and the tumor yields were 4.0 tumors per mouse in the former group and 9.8 per mouse in the latter group in week 30. We confirmed, through this experiment, that teleocidin is as potent as TPA in in vivo two-stage carcinogenesis in mouse skin. These two structurally unrelated classes, indole alkaloid and phorbol ester, showed tumor promoting activity in almost the same range.