Gaofeng Wang, PhD

Associate Professor of Human Genetics
University of Miami Miller School of Medicine, Miami, FL

 image of Dr. Gaofeng Wang
Abstract: Recent advances have uncovered a previously unknown function of vitamin C in regulating the demethylation of DNA and histones. Ten-eleven translocation (TET) dioxygenases initiate DNA demethylation by converting 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). Vitamin C is essential for the function of TET by providing Fe(II), a cofactor of TET. Loss of 5hmC is accompanied with malignant cellular transformation. Overexpressing TET can partially re-establish a normal 5hmC profile in cancer cells and represses their malignancy. While overexpressing TETs in patients might not be clinically feasible, these discoveries suggest that finding a means of restoring normal 5hmC content may yield a novel therapy for cancer. The expression of vitamin C transporter SVCT2 is frequently downregulated in cancer. For instance, SVCT2 expression is decreased in 72.5% of breast cancer cases by at least 1.5-fold compared to the matched normal breast tissues. This suggest it is necessary to compensate the downregulated SVCT2 with vitamin C supplements in risk population and cancer patients. Treatment of cancer cells with vitamin C increases 5hmC content and results in a markedly shifted transcriptome. These changes are correlated with decreased cellular malignant phenotypes. Furthermore, by promoting the demethylation of DNA and histones, vitamin C changes the response of cancer treatment. For example, vitamin C improves the efficacy of Bromodomain and extraterminal domain inhibitors (BETi) in treating melanoma. In conclusion, vitamin C can prevent cancer initiation and progression by reestablishing 5hmC. Vitamin C also can improve the response of certain cancer drugs.