West-Libyan propolis and rosemary have synergistic anti-tumor effect against 12-O-tetradecanoylphorbol 13-acetate-induced skin tumor in BULB/C mice previously initiated with 7,12-dimethylbenz[a]anthracene

Abstract

Background and aim: Many dietary constituents are chemopreventive in animal models and experiments with cultured cells are revealing various potential mechanisms of action. Many of these compounds can prevent, or greatly reduce, initiation of carcinogenesis, or can act on cell proliferation. In this study we examined the effects of topical application of propolis extract, rosemary extract and a mixture of both extracts together on 12-O-tetradecanoylphorbol 13-acetate-induced tumor promotion in mice previously initiated with 7,12-dimethylbenz[a]anthracene. Methods: The propolis extract, rosemary extract and a mixture of both extracts together were applied topically 15 min prior to the application of 5 nmol TPA for 20 weeks. Results: A decrease in the number of skin tumors per mouse by 27, 39, 71% was seen, as well as a decrease in the number of mice with tumors by 22, 31, 75% and inhibited the tumor size per mouse by 46, 62, 72% for propolis, rosemary and both together respectively. Also TUNEL data showed more increased incidence of TUNEL positivity among cancer cells in both topical applications together than their separate application on the back skin of mice. Conclusions: It is likely that the combination of their activities such as antioxidant and cytotoxic ones as well as the combination of several components in both are responsible for their inhibitory effect on carcinogenesis. Further investigations are recommended in order to establish the conditions under which topical application of propolis as well as rosemary produces either protective or deleterious effects.