MOLECULAR SIGNATURES OF SOY-DERIVED PHYTOCHEMICALS IN ANDROGEN-RESPONSIVE PROSTATE CANCER CELLS: A COMPARISON STUDY USING DNA MICROARRAY

Authors: TAKAHASHI, YOKO - NAT'L FD INST., JAPAN; LAVIGNE, JACKIE - NCI/NIH, BETHESDA, MD; HURSTING, STEPHEN - NCI/NIH, BETHESDA, MD; CHANDRAMOULI, GADISETTI - NCI/NIH, BETHESDA, MD; PERKINS, SUSAN - NCI/NIH, BETHESDA, MD; KIM, YOUNG - NCI/NIH, BETHESDA, MD; Wang, Thomas - Tom

Submitted to: Molecular Carcinogenesis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/18/2006
Publication Date: 12/13/2006
Citation: Takahashi, Y., Lavigne, J.A., Hursting, S.D., Chandramouli, G.V., Perkins, S.N., Kim, Y.S., Wang, T.T. 2006. Molecular signatures of soy-derived phytochemicals in androgen-responsive prostate cancer cells: a comparison study using dna microarray. Molecular Carcinogenesis. 12:943-956.

Interpretive Summary: Many studies have correlated the consumption of soy-rich diets with a decreased risk of developing hormone-dependent cancers, including prostate cancer. Question remains what may be the active phytochemical that contribute to cancer preventive effects and their mechanism. To better understand the molecular mechanisms underlying the beneficial effects of soy-derived phytochemcials on prostate cancer prevention, we utilized a DNA microarray approach to examine the effects of daidzein and equol, at doses in the physiologic range, on global gene expression patterns in androgen-dependent cancer cells. The data was then compared with previous generated data on genistein, another soy-derived phytochemcial. DNA microarray analyses were performed on androgen-dependent LNCaP human prostate cancer cells exposed to 0, 1, 5 or 25 'M of equol, daidzein or genistein. We found a concentration-dependent modulation of multiple cellular pathways that are important in prostate carcinogenesis. Interestingly, the androgen receptor-mediated pathways, in particular, appeared to be modulated by all three compounds at the lowest concentrations. Exposure to the male sex hormone androgen is considered risk factor for development of prostate cancer. Based on these results, we proposed that the regulation of androgen receptor-mediated is potentially the most relevant chemopreventive mechanism for soy phytochemcials administered at physiologic levels. This work provide novel information for cancer research scientist regarding molecular targets and mechanism(s) of action of soy-derived phytochemical(s) and will serve as important bases for future design of cancer preventive strategy.

Technical Abstract: The present study utilized microarray technology as a tool to elucidate the molecular signatures of soy-derived phytochemicals in the human androgen-responsive prostate cancer cell line LNCaP. Global gene expression pattern analysis of LNCaP cells exposed to 0, 1, 5 or 25 'M 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. Multidimensional 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, including the cell cycle pathway genes. However, the three compounds also exerted similar effect on genes belonging to several other important cellular pathways. A universal effect of the three compounds on androgen-responsive genes, IGF-1 pathway gene and MAP kinase-related pathway gene 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.