132. The protein kinase inhibitor staurosporine induces differentiation of neoplastic mouse keratinocytes in vitro and blocks their growth as benign epidermal tumors in vivo

Abstract

Salvia libanotica (sage) extract is a popular plant remedy used by Middle Eastern people to treat common complaints such as colds and abdominal pain. In this study, the chemopreventive effects of sage oil on 7,12 dimethylbenz[a]anthracene (DMBA)-initiated and 12-0-tetradecanoylphorbol-13-acetate (TPA)-promoted skin papillomas was investigated. Furthermore, its growth inhibitory and cytotoxic effects on a mouse papilloma-derived cell line (SP-1) were studied using 3H-thymidine incorporation, cell count and trypan blue dye exclusion assays. Sage oil was either applied topically to mouse skin at concentrations of 5, 50 and 100 % in acetone, injected intraperitonealy at concentrations of 4 (37 mg/ml) and 8 % (75 mg/ml) in saline or given by gavage at 100 % twice per week for 20 weeks, 20 minutes prior to each promotion treatment with TPA. The topically applied 100 % oil extract delayed tumor appearance by 4 weeks and inhibited tumor incidence and yield by 19 and 61 %, respectively, at week 20. Topical application of 50 % and 5 % sage oil inhibited tumor yield by 41 % at week 20. Tumor weight was decreased by 75 % and 80 % following treatment of mouse skin with 50 % and 100 % oil, respectively. Intraperitoneal injections and gavage treatments failed to inhibit the promotion of tumors in mouse skin, but significantly decreased tumor weight and volume. Sage oil displayed strong growth inhibitory effects on the SP-1 papilloma derived cell line following 24 hrs of treatment with estimated IC50 of 50 μg/ml. This observed growth inhibition was due to cytostatic and not cytotoxic effects. Our results suggest that the oil extract of the sage plant has potent suppressive activities against tumor promotion in mouse skin and thus could be an effective chemopreventive agent against skin cancer.