Tephrosia purpurea alleviates phorbol ester-induced tumor promotion response in murine skin

In recent years, considerable emphasis has been placed on identifying new c ancer chemopreventive agents, which could be useful for the human populatio n. Tephrosia purpurea has been shown to possess significant activity agains t hepatotoxicity, pharmacological and physiological disorders. Earlier we s howed that Tephrosia purpurea inhibits benzoyl peroxide-mediated cutaneous oxidative stress and toxicity. In the present study, we therefore assessed the effect of Tephrosia purpurea on 12-O-tetradecanoyl phorbal-13-acetate ( TPA; a well-known phorbol eater) induced cutaneous oxidative stress and tox icity in murine skin. The pre-treatment of Swiss albino mice with Tephrosia purpurea prior to application of croton oil (phorbol ester) resulted in a dose-dependent inhibition of cutaneous carcinogenesis. Skin tumor initiatio n was achieved by a single topical application of 7,12-dimethyl benz(a)anth racene (DMBA) (25 mug per animal per 0.2 mi acetone) to mice. Ten days late r tumor promotion was started by twice weekly topical application of croton oil (0.5% per animal per 0.2 ml acetone, v/v). Topical application of Teph rosia purpurea 1 h prior to each application of croton oil (phorbol ester) resulted in a significant protection against cutaneous carcinogenesis in a dose-dependent manner. The animals pre-treated with Tephrosia purpurea show ed a decrease in both tumor incidence and tumor yield as compared to the cr oton oil (phorbol ester)-treated control group. In addition, a significant reduction in TPA-mediated induction in cutaneous ornithine decarboxylase (O DC) activity and [H-3]thymidine incorporation was also observed in animals pre-treated with a topical application of Tephrosia purpurea. The effect of topical application of Tephrosia purpurea on TPA-mediated depletion in the level of enzymatic and non-enzymatic molecules in skin was also evaluated and it was observed that topical application of Tephrosia purpurea Frier to TPA resulted in the significant recovery of TPA-mediated depletion in the level of these molecules, namely glutathione, glutathione S-transferase, gl utathione reductase and catalase. From these data we suggest that Tephrosia purpurea can abrogate the tumor-promoting effect of croton oil (phorbol es ter) in murine skin. (C) 2001 Academic Press.