Cheiranthus cheiri Abrogates Phorbol Ester Induced Tumor Promotion Response in Murine Skin

Abstract

Cancer chemoprevention has become an important area of cancer research for identifying new potentially useful inhibitors of carcinogenesis. Cheiranthus cheiri has been shown to possess significant activity against various physiological disorders. In the present communication, we assessed the effect of Cheiranthus cheiri on 12- O -tetradecanoyl 13-phorbol acetate (TPA)-induced cutaneous oxidative stress and toxicity in murine skin. The pretreatment of Swiss albino mice with Cheiranthus cheiri prior to application of croton oil (phorbol ester) resulted in a dose-dependent inhibition of cutaneous carcinogenesis. Skin tumor initiation was achieved by a single topical application of 7,12-dimethyl benz (a) anthracene (DMBA) (40 µg/animal/0.2 ml acetone) to mice. Ten days later tumor promotion was started by twice weekly topical application of croton oil (1.0%/animal/0.2 ml acetone, v/v). Topical application of Cheiranthus cheiri 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 pretreated with Cheiranthus cheiri showed a significant decrease in both tumor incidence and tumor yield as compared to croton oil (phorbol ester)-treated control group (p < 0.05). In addition a significant reduction in TPA-mediated induction in cutaneous ornithine decarboxylase (ODC) activity and [3 H]-thymidine incorporation was also observed in animals pretreated with topical application of Cheiranthus cheiri (p < 0.05). Prophylactic treatment of mice with Cheiranthus cheiri 1 h before TPA (20 nmol/animal/0.2 ml acetone) treatment resulted in the diminution of TPA-mediated cutaneous oxidative stress. It was observed that topical application of Cheiranthus cheiri prior to TPA resulted in the significant recovery of TPA-mediated depletion in the level and activities of cellular anti-oxidants, viz, glutathione reduced, glutathione S -transferase, glutathione reductase, glutathione peroxidase and catalase (p < 0.05). From these data, we suggest that Cheiranthus cheiri can abrogate the tumor promoting effect of croton oil (phorbol ester) in murine skin.