Administration of resveratrol enhances cell-cycle arrest followed by apoptosis in DMBA-induced skin carcinogenesis in male Wistar rats

Y.-Q. Hu, J. Wang, J.-H. Wu

Department of Dermatology, Changhai Hospital, Second Military Medical University, Shanghai, P.R. China. jhwu71@yahoo.com

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• Pharmacology

OBJECTIVE: Resveratrol (RES), present in fruits and plants, is a natural compound that has been shown various medicinal properties, including protection of cardiovascular disease and cancer risk. However, the effects of RES on skin cancer have not been investigated. The present work was designed to explore the anticancer potential of RES against chemical-induced skin carcinogenesis in rats.

MATERIALS AND METHODS: Skin carcinogenesis were induced in male Wistar rats by a single topical application of 7,12-dimethylbenz(a)anthracene (DMBA) and 2 weeks later, 12-O-tetradecanoylphorbol-13-acetate (TPA) were topically applied thrice a week to promote skin carcinogenesis. RES at a dose of 1 or 2 mg/kg body weight/week were administered to DMBA treated rats. The effects of RES on DMBA-modified cell-cycle arrest, apoptosis and protein expressions were analyzed by flow cytometry, immunohistochemistry and Western blot, respectively.

RESULTS: RES treatment caused a significant reduction of DMBA-induced tumor occurrence, tumor volume and tumor weight, as compared to DMBA control group. Further, RES treatment increases G2/M arrest and apoptosis by modulating cell-cycle and apoptosis regulated genes such as p53, p21, caspase-3, bax, survivin, cyclin-B and cdc-2 when compared with DMBA control group.

CONCLUSIONS: Taken together, the anticancer effect of RES is associated with regulation of cell-cycle and apoptosis in skin cancer, thereby attenuating skin cancer growth. Hence, these findings suggest that RES may be a therapeutic agent for skin cancer treatment.

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