Using DNA microarray analyses to elucidate the effects of genistein in androgen-responsive prostate cancer cells: identification of novel targets.
Many studies have correlated the consumption of soy-rich diets with a decreased risk of developing hormone-dependent cancers, including prostate cancer. Genistein is a candidate prostate cancer preventive phytochemical found at high levels in soybean and soy foods. To better understand the molecular mechanisms underlying the beneficial effects of genistein on prostate cancer prevention, we used a DNA microarray approach to examine the effects of genistein at concentrations in the physiologic range on global gene expression patterns in androgen-responsive cancer cells. Microarray analyses were performed on androgen-responsive LNCaP human prostate cancer cells exposed to 0, 1, 5, or 25 microM genistein. We found a concentration-dependent modulation of multiple cellular pathways that are important in prostate carcinogenesis. Interestingly, the androgen receptor (AR)-mediated pathways, in particular, appeared to be modulated by genistein at the lowest concentrations. Based on these results, we propose that the regulation of AR-mediated pathways is potentially the most relevant chemopreventive mechanism for genistein administered at physiologic levels.
Takahashi
Yoko
Y
Phytonutrients Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service/ USDA, Beltsville, MD 20705, USA.
Lavigne
Jackie A
JA
Hursting
Stephen D
SD
Chandramouli
Gadisetti V R
GV
Perkins
Susan N
SN
Barrett
J Carl
JC
Wang
Thomas T Y
TT
D016588:Anticarcinogenic Agents / Q000494:pharmacology; D002453:Cell Cycle; D004249:DNA Damage; D019833:Genistein / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000517:prevention & control; D011944:Receptors, Androgen / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear; D015398:Signal Transduction; D013312:Stress, Physiological; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
D016588:Anticarcinogenic Agents; D011944:Receptors, Androgen; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D007334:Insulin-Like Growth Factor I; D019833:Genistein