Tephrosia purpurea alleviates phorbol ester-induced tumor promotion response in murine skin.
In recent years, considerable emphasis has been placed on identifying new cancer chemopreventive agents, which could be useful for the human population. Tephrosia purpurea has been shown to possess significant activity against hepatotoxicity, pharmacological and physiological disorders. Earlier we showed 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 ester) induced cutaneous oxidative stress and toxicity 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 initiation was achieved by a single topical application of 7,12-dimethyl benz(a)anthracene (DMBA) (25 microg per animal per 0.2 ml acetone) to mice. Ten days later 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 Tephrosia 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 showed a decrease in both tumor incidence and tumor yield as compared to the croton oil (phorbol ester)-treated control group. In addition, a significant reduction in TPA-mediated induction in cutaneous ornithine decarboxylase (ODC) activity and [3H]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 prior to TPA resulted in the significant recovery of TPA-mediated depletion in the level of these molecules, namely glutathione, glutathione S-transferase, glutathione reductase and catalase. From these data we suggest that Tephrosia purpurea can abrogate the tumor-promoting effect of croton oil (phorbol ester) in murine skin.
Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
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Saleem
Ahmed Su
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Alam
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Sultana
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology*; D003436:Croton Oil / Q000494:pharmacology; D003879:Dermatologic Agents / Q000494:pharmacology; D005978:Glutathione / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D009955:Ornithine Decarboxylase / Q000187:drug effects* / Q000378:metabolism; D010703:Phorbol Esters / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D012867:Skin / Q000187:drug effects / Q000201:enzymology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology
D000975:Antioxidants; D002273:Carcinogens; D003879:Dermatologic Agents; D010703:Phorbol Esters; D010936:Plant Extracts; D015127:9,10-Dimethyl-1,2-benzanthracene; D003436:Croton Oil; D009955:Ornithine Decarboxylase; D005978:Glutathione