Inhibition of 7,12-dimethylbenz(A)anthracene-induced Skin Tumorigenesis in C57bl/6 Mice by Sulforaphane is Mediated by Nuclear Factor E2-related Factor 2.
From: Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Cancer research
- Publish Date: Aug 2006
- ISSN: 1538-7445
- Volume: 66
- Issue: 16
- Pages: 8293-6
- Medium: Internet
- Language: English
- Citation (JAMA): Xu Changjiang, Huang Mou-Tuan, Shen Guoxiang, et al. Inhibition of 7,12-dimethylbenz(A)anthracene-induced Skin Tumorigenesis in C57bl/6 Mice by Sulforaphane is Mediated by Nuclear Factor E2-related Factor 2.. Cancer Res. Aug 2006;66:8293-6
Abstract
Sulforaphane, a dietary isothiocyanate, possesses potent chemopreventive effects through the induction of cellular detoxifying/antioxidant enzymes via the transcription factor nuclear factor E2-related factor 2 (Nrf2). To investigate carcinogenesis mechanisms related to the regulation of Nrf2, we examined the tumor incidence and tumor numbers per mouse in Nrf2 wild-type (+/+) and Nrf2 knockout (-/-) mice. 7,12-Dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate treatments resulted in an increase in the incidence of skin tumors and tumor numbers per mouse in both genotypes; however, both indices were markedly higher in Nrf2(-/-) mice as compared with Nrf2(+/+) mice. Western blot analysis revealed that Nrf2 as well as heme oxygenase-1, a protein regulated by Nrf2 were not expressed in skin tumors from mice of either genotype, whereas expression of heme oxygenase-1 in Nrf2(+/+) mice was much higher than that in Nrf2(-/-) mice in nontumor skin samples. Next, we examined the chemopreventive efficacy of sulforaphane in mice with both genotypes. Topical application of 100 nmol of sulforaphane once a day for 14 days prior to 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate applications decreased the incidence of skin tumor in the Nrf2(+/+) mice when compared with the vehicle-treated group. Importantly, there was no chemoprotective effect elicited by sulforaphane pretreatment in the Nrf2(-/-) mice group. Taken together, our results show for the first time that Nrf2(-/-) mice are more susceptible to skin tumorigenesis and that the chemopreventive effects of sulforaphane are mediated, at least in part, through Nrf2.
Mesh Headings (Keywords): 9,10-Dimethyl-1,2-benzanthracene, Animals, Anticarcinogenic Agents, DNA, Neoplasm, Disease Susceptibility, Mice, Mice, Inbred C57BL, Mice, Knockout, NF-E2 Transcription Factor, Polymerase Chain Reaction, Skin Neoplasms, Thiocyanates
Check for Full Text / PubMed Unique Identifier (PMID): 16912211
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