Gene Expression Changes Induced by Genistein in the Prostate Cancer Cell Line LNCaP

Abstract

Epidemiological evidence suggests that soy consumption is associated with a decreased risk of prostate cancer. The isoflavone genistein is found at high levels in soy and a large body of evidence suggests it is important in mediating the cancer preventive effects of soy. The mechanisms through which genistein acts in prostate cancer cells have not been fully defined. We used gene expression profiling to identify genes significantly modulated by low and high doses of ge- nistein in LNCaP cells. Significant genes were identified using StepMiner analysis and significantly altered pathways with Ingenuity Pathways analysis. Genistein significantly altered expression of transcripts involved in cell growth, carcinogen defenses and steroid signaling pathways. The effects of genistein on these pathways were confirmed by directly assessing dose-related effects on LNCaP cell growth, NQO-1 enzymatic activity and PSA protein expression. Genistein produces diverse effects on gene expression that are dose-dependent and this has important implications in developing genistein as a putative prostate cancer preventive agent.