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Reactivation of tumor suppressor genes (TSGs) involved in carcinogenesis by nontoxic bioactive food component represents a promising strategy for cancer chemoprevention. Recently, curcumin has been demonstrated to inhibit a bacterial DNA methyltransferase (M. Sss I) activity, induce global DNA hypomethylation in leukemia cells, and reactivate several hypermethylation silenced genes in lung and prostate cancer cells. Herein, we demonstrated that curcumin can enhance the mRNA and protein levels of ras-association domain family protein 1A (RASSF1A), 1 hypermethylation-silenced TSG, and decrease its promoter methylation in breast cancer cells. Mechanistic study demonstrated that curcumin can decrease DNA methylation activity of nuclear extract and downregulate the mRNA and protein levels of DNMT1 in MCF-7 cells, which may be associated with curcumin-induced disruption of NF-κB/Sp1 complex bound to the promoter region of DNMT1. Altogether, this study reveals a novel molecular mechanism of curcumin as a chemo-preventive agent for breast cancer through hypomethylation reactivation of RASSF1A. [ABSTRACT FROM PUBLISHER]

Diet may be a modifier of smoking-related cancer risk, with protective effects of intake of fruits and vegetables and associated antioxidants found in many observational studies. We previously reported serum Beta-Cryptoxanthin levels being inversely associated with smoking-related lung cancer incidence in a cohort of Chinese men. We noted, however, that serum Beta-Cryptoxanthinn is negatively correlated with smoking. Since self-reports of smoking intensity undoubtedly contain errors, this negative correlation indicates a potential bias in assessing the effects of Beta-Cryptoxanthin, due to confounding with the unmeasured (residual) portion of cigarette exposure. We evaluated cotinine levels in pre-diagnostic spot urine samples to attempt to improve smoking assessment. We noted that urinary cotinine levels correlated significantly with cigarette consumption overall and that cotinine was strongly predictive of lung cancer risk. Urinary cotinine, however, was not as strong a predictor of lung cancer risk in current smokers as were self-reports of cigarette consumption and cotinine remained only a marginally significant predictor of lung cancer risk after adjustment for self-reports. An apparent benefit of Beta-Cryptoxanthin remained evident when including both urinary cotinine and self-reported cigarette consumption and cotinine in the statistical model. However, we conclude that cotinine measured from a single spot urine seems to have only limited value in augmenting self-reports of cigarette consumption so that, at present, the apparent protective effects of Beta-Cryptoxanthinn, as seen in our own study, should continue to be regarded as unproven. We believe that future epidemiological evaluation of the association between Beta-Cryptoxanthin (and other antioxidants) and reduced lung cancer risk must utilize improved biomarkers to augment smokers' own self-reports of smoking amount. [ABSTRACT FROM AUTHOR]