stevioside and Skin-Neoplasms

In a search for potential cancer chemopreventive agents from natural resources, stevioside (1), a sweetener, and six related compounds, including two aglycones steviol (6) and isosteviol (7), were screened in an in vitro assay for inhibitory effects on Epstein-Barr virus early antigen activation. Compounds 1, 6 and 7 showed significant activity in this assay and also exhibited strong inhibitory effects in a two-stage carcinogenesis test using mouse skin induced by 7,12-dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA). The inhibitory effects of these three compounds were greater than that of glycyrrhizin. Furthermore, these three compounds significantly inhibited mouse skin carcinogenesis initiated by peroxynitrite and promoted by TPA. Their activities were comparable to that of curcumin. These results suggested that 1, as well as 6 and 7, could be valuable as chemopreventive agents for chemical carcinogenesis.

Topics: Animals; Antineoplastic Agents; Carcinogenicity Tests; Chemoprevention; Curcumin; Diterpenes, Kaurane; Glucosides; Glycyrrhizic Acid; Herpesvirus 4, Human; Mice; Skin Neoplasms

Four steviol (ent-kaurene-type diterpenoid) glycosides, stevioside, rebaudiosides A and C, and dulcoside A, have been isolated from Stevia rebaudiana BERTONI. These compounds showed strong inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice. The 50% inhibitory dose of these compounds for TPA-induced inflammation was 54.1-291.6 micro g/ear. Furthermore, at 1.0 and 0.1 mg/mouse of stevioside mixture, the mixture of these compounds markedly inhibited the promoting effect of TPA (1 micro g/mouse) on skin tumor formation initiated with 7,12-dimethylbenz[a]anthracene (50 micro g/mouse).

Topics: Animals; Antineoplastic Agents, Phytogenic; Diterpenes; Diterpenes, Kaurane; Drug Screening Assays, Antitumor; Female; Glucosides; Mice; Mice, Inbred ICR; Skin Neoplasms; Stevia; Tetradecanoylphorbol Acetate