The Nrf2-/- mice are more prone to carcinogen-induced skin, colon and other cancers and are more susceptible to DSS-induced colon inflammation and DSS-AOM-induced colon carcinogenesis. Inhibition of LPS-induced inflammation in mouse macrophages by sulforaphane (SFN) would require Nrf2. Epigenetically, in the prostate TRAMP tumors, as cancer progresses, a shut-down of Nrf2 via CpG methylation of the promoter region, attenuating Nrf2-mediated genes, which were reversed by dietary PEITC, curcumin and tocopherols. Curcumin could demethylate CpGs of Nrf2 promoter in TRAMP C1 cells and Neurog1 promoter in LNCaP cells, which would impact early carcinogenesis and later stages of cancer development. Hence, nutritional phytochemicals can confer early chemopreventive epigenetic effects resulting in blocking initiation/promotion of carcinogenesis, as well as late stage of epigenetic effects inhibiting progression of carcinogenesis.
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