Title: Modulation of gene methylation by genistein or lycopene in breast cancer cells.
Authors: King-Batoon, Audrey; Leszczynska, Joanna M; Klein, Catherine B
Published In Environ Mol Mutagen, (2008 Jan)
Abstract: Dietary agents with chemopreventive potential, including soy-derived genistein and tomato-derived lycopene, have been shown to alter gene expression in ways that can either promote or potentially inhibit the carcinogenic processes. To begin to explore the mechanisms by which these agents may be acting we have examined the DNA methylation modulating capacity of genistein or lycopene for several genes relevant to breast cancer in the breast cancer cell lines MCF-7 and MDA-MB-468, as well as in immortalized but noncancer fibrocystic MCF10A breast cells. We find using methylation specific PCR (MSP) that a low, nontoxic concentration of genistein (3.125 microM, resupplemented every 48 hr for 1 week) or a single dose of lycopene (2 microM) partially demethylates the promoter of the GSTP1 tumor suppressor gene in MDA-MB-468 cells. RT-PCR studies confirm a lack of GSTP1 expression in untreated MDA-MB-468, with restoration of GSTP1 expression after genistein or lycopene treatment. The RARbeta2 gene however, was not demethylated by genistein or lycopene in either of these breast cancer cell lines. But, lycopene (2 microM, once per week for 2 weeks) did induce demethylation of RARbeta2 and the HIN-1 genes in the noncancer MCF10A fibrocystic breast cells. These data show for the first time that the tomato carotenoid lycopene has direct DNA demethylating activity. In summary, both genistein and lycopene, at very low, dietarily relevant concentrations can potentially mitigate tumorigenic processes via promoter methylation modulation of gene expression.
PubMed ID: 18181168
MeSH Terms: Breast Neoplasms/drug therapy; Breast Neoplasms/genetics*; Carotenoids/pharmacology*; Cell Line, Tumor; Cell Proliferation; DNA Methylation/drug effects*; Dose-Response Relationship, Drug; Female; Gene Expression Regulation, Neoplastic/drug effects*; Genistein/pharmacology*; Glutathione S-Transferase pi/drug effects; Glutathione S-Transferase pi/genetics; Humans; Reverse Transcriptase Polymerase Chain Reaction