|Wang, Thomas - Tom|
Submitted to: UJNR Food & Agricultural Panel Proceedings
Publication Type: Proceedings
Publication Acceptance Date: 8/25/2005
Publication Date: 10/22/2005
Citation: Wang, T.T., Kim, Y.S., Hursting, S.D., Perkins, S.N., Gadisetti, C.R., Lavigne, J.A., Takahashi, Y. 2005. Deciphering molecular signatures of phytochemicals in cells. UJNR Food & Agricultural Panel Proceedings. Interpretive Summary: Health beneficial effects of phytochemicals are well documented. However, the mechanisms by which these compounds provide protection against diseases, such as cancer, are unclear. To better design a health beneficial dietary strategy, it is important to understand how phytochemicals work. We proposed that deciphering the molecular targets, i.e., molecular signatures of phytochemicals in target cells, would be important in addressing this question. In this study, we utilized a DNA microarray approach to examine the effects of the cancer preventive soy phytochemicals equol, daidzein, and genistein, at doses in the physiologic range, on global gene expression patterns in androgen-dependent prostate cancer cells. Based on the expression results, we proposed that the regulation of male sex hormone-mediated events is potentially the most relevant chemopreventive mechanism for soy phytochemicals administered at physiologic levels. This work provides novel information for cancer research scientist regarding molecular targets and mechanism(s) of action of soy-derived phytochemical(s) and will serve as an important basis for future design of cancer preventive dietary strategy.
Technical Abstract: The present study utilizes microarray technology as a tool to elucidate the molecular signatures of soy-derived phytochemcials in the LNCaP human androgen-responsive prostate cancer cell line. Global gene expression pattern analyses of LNCaP cells exposed to 0, 1, 5, or 25 microM of the soy-derived phytochemicals equol and daidzein were conducted and compared. The data were further compared with previously generated data from exposure of LNCaP cells to the same doses of genistein, a soy isoflavone. Multi-dimensional scaling analyses of the expression patterns suggest that these compounds exerted differential effects on gene expression in LNCaP cells. Further examination of specific gene changes revealed that these compounds differentially modulated genes in multiple cellular pathways. However, the three compounds also exerted similar effects on genes belonging to several other important cellular pathways. A universal effect on adrogen-responsive genes of the three compounds was observed. These results provide the foundation for establishing molecular signatures for equol, daidzein, and genistein. Moreover, these results also allow for the identification of candidate mechanism(s) by which soy phytochemicals and soy may act in prostate cancer cells.