Abstract 658: Identification of a molecular signature after L-methionine treatment in MCF-7 and LNCaP cancer cells

Abstract

Abstract Our previous research has shown that the essential sulfur-amino acid methionine inhibited proliferation of breast and prostate cancer cell lines, concomitant with p53 modification. The aim of this study was to increment understanding of the mechanisms underlying these effects by determining the influence of L-methionine on functional molecular signatures in these cell lines. Wild-type p53-expressing MCF-7 (breast cancer) and LNCaP (prostate cancer) cells were treated with L-methionine (5mg/ml) for 72hrs. Changes in molecular signatures of these cells were examined by microarray analysis of 15,814 probes in triplicate samples. Genes with significant expression changes were identified by False Discovery Rate analysis (p-value < 0.01; fold-change > 1.5). In LNCaP cells, 325 genes were up-regulated by methionine treatment and 517 genes down-regulated. In MCF-7 cells, 86 genes were up-regulated by methionine and 135 genes up-regulated. Ninety eight genes were regulated in the same direction by methionine in both cell lines; 10 of these genes were up-regulated (AFF3, AKR1C2, ATF3, C8ORF4, GPX8, LAMA3, RBM4B, NQO1, SH3BGRL, and VAMP5) and 88 genes were down-regulated. The expression of five other genes (H1F0, TNF, CENPN, ACAT2, and DHRS2) was changed in opposite directions in the two cell lines. Increases in expression were verified by quantitative RT-PCR. Several of the up-regulated genes encode proteins involved in cellular redox regulation and many of the down-regulated genes belonged to protein kinase families. These observations suggest that methionine is an enhancer of antioxidant activities and has potential as an anti-cancer agent that targets breast and prostate cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 658.