期刊
MOLECULAR NUTRITION & FOOD RESEARCH
卷 54, 期 10, 页码 1486-1496出版社
WILEY
DOI: 10.1002/mnfr.201000105
关键词
c-myc; Colorectal cancer; Ornithine decarboxylase; Sulforaphane; Transforming growth factor-beta signaling
资金
- DFG
Scope: The objective of this study was to elucidate molecular mechanisms behind the antitumor activities of the isothiocyanate sulforaphane (SFN) in colorectal cancer cells. Methods and results: Cell growth was determined by BrdU incorporation and crystal violet staining. Protein levels were examined by Western blot analysis. Ornithine decarboxylase (ODC) activity was assayed radiometrically. Reverse transcriptase-PCR was used for measuring mRNA expression. For reporter gene assays plasmids were transfected into cells via lipofection and luciferase activity was measured luminometrically. Acetyl-histone H3 and H4 chromatin immunoprecipitation (ChIP) assays were performed followed by PCR with TGF-beta-receptor II promoter specific primers. We could show that SFN-mediated cell growth inhibition closely correlates with a dose-dependent reduction of protein expression and enzymatic activity of ODC. This effect seems to be due to reduced protein levels and trans-activation activity of transcription factor c-myc, a direct regulator of ODC expression, as a consequence of SFN-induced TGF-beta/Smad signaling. The coherency of these results was further confirmed by using TGF-beta receptor kinase inhibitor SB431542, which largely abolishes inhibitory effects of SFN on both, ODC activity and cell growth. Conclusion: Since elevated ODC enzyme activity is associated with enhanced tumor development, SFN may be a dietary phytochemical with potential to prevent carcinogenesis.
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