Methyl donor nutrients inhibit the growth of human breast cancer cells

Abstract

Lipotropes (methyl donor nutrients) are involved in one-carbon metabolism including DNA methylation. Hypermethylation of CpG islands within promoter regions of genes is associated with transcriptional inactivation of the gene. Methyl donors may alter the expression of apoptosis-related genes via alterations in DNA methylation and consequently increase the sensitivity of cancer cells to apoptosis. To investigate the effects of lipotropes on breast cancer cell growth and apoptosis, two estrogen receptor-positive breast cancer cell lines, MCF-7 and T47D, as well as a normal mammary cell line, MCF-10A, were cultured in control, lipotrope-supplemented, tamoxifen (TAM), and lipotrope-supplemented plus TAM treatment media. Cell proliferation was measured by a tetrazolium salt reduction assay. Lipotrope supplementation inhibited the growth of both T47D (P < 0.01) and MCF-7 (P < 0.01) cell lines. All treatment groups, except the control groups in all cell lines, demonstrated morphological changes, as assessed by DAPI staining, consistent with apoptotic cell death. Lipotropes significantly decreased the Bcl-2 protein level, quantified by an enzyme immunometric assay, in the T47D cell line (P = 0.01) but not in the MCF-7 cell line. These results show that lipotrope supplementation may be useful in the development of a nutritional strategy for human breast cancer therapy. Supported by NIH-NCI (# R01CA78179-01).