title: Soy isoflavones and prostate cancer: a review of molecular mechanisms.
abstract: Soy isoflavones are dietary components for which an association has been demonstrated with reduced risk of prostate cancer (PCa) in Asian populations. However, the exact mechanism by which these isoflavones may prevent the development or progression of PCa is not completely understood. There are a growing number of animal and in vitro studies that have attempted to elucidate these mechanisms. The predominant and most biologically active isoflavones in soy products, genistein, daidzein, equol, and glycetin, inhibit prostate carcinogenesis in some animal models. Cell-based studies show that soy isoflavones regulate genes that control cell cycle and apoptosis. In this review, we discuss the literature relevant to the molecular events that may account for the benefit of soy isoflavones in PCa prevention or treatment. These reports show that although soy isoflavone-induced growth arrest and apoptosis of PCa cells are plausible mechanisms, other chemo protective mechanisms are also worthy of consideration. These possible mechanisms include antioxidant defense, DNA repair, inhibition of angiogenesis and metastasis, potentiation of radio- and chemotherapeutic agents, and antagonism of estrogen- and androgen-mediated signaling pathways. Moreover, other cells in the cancer milieu, such as the fibroblastic stromal cells, endothelial cells, and immune cells, may be targeted by soy isoflavones, which may contribute to soy-mediated prostate cancer prevention. In this review, these mechanisms are discussed along with considerations about the doses and the preclinical models that have been used.
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA. Electronic address: amahmo4@uic.edu.
authors.forename: Abeer M
authors.initials: AM
authors.lastname: Mahmoud
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA; Department of Pathology, Xinxiang Medical University, Xinxiang, China.
authors.forename: Wancai
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Maarten C
authors.initials: MC
authors.lastname: Bosland
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D004260:DNA Repair; D044127:Epigenesis, Genetic; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D007529:Isoflavones / Q000627:therapeutic use*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000188:drug therapy; D014411:Neoplastic Stem Cells / Q000187:drug effects; D011453:Prostaglandins / Q000502:physiology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000517:prevention & control*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D011944:Receptors, Androgen / Q000187:drug effects; D011960:Receptors, Estrogen / Q000187:drug effects; D015398:Signal Transduction; D013025:Glycine max / Q000737:chemistry*; D016212:Transforming Growth Factor beta / Q000502:physiology; D060449:Wnt Signaling Pathway / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D000975:Antioxidants; D007529:Isoflavones; D035683:MicroRNAs; D011453:Prostaglandins; D011838:Radiation-Sensitizing Agents; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I; D011505:Protein-Tyrosine Kinases
keywords: APC; APE1/Ref; APK; B-cell translocation gene; BTG; CSC; CSF; Chemoprevention; DSH; ECGF1; EPHB; FAK; GADD; GM-CSF; GPx; GSK3β; GSR; GSTP; GSk-3β; Genistein; HAT; Isoflavone; LEF; LHRH; N-benzyloxycarbonyl-Val-Asp-fluoromethyl-ketone; Prostate cancer; RASSF; TAMs; TRIM; activated protein kinase; adenomatous polyposis coli; apurinic apyrimidinic endonuclease redox effector factor; cancer stem cells; colony-stimulating factor; disheveled; endothelial cell growth factor; ephrin B; focal adhesion kinase; glutathione S-transferase P; glutathione peroxidase; glutathione reductase; glycogen synthase kinase 3β; glycogen synthase kinase-3β; granulocyte monocyte-colony stimulating factor; growth arrest and DNA damage; histone acetyltransferases; luteinizing hormone releasing hormone; lymphoid enhancer factor; ras association domain family; tripartite motif-containing protein; tumor associated macrophages; uPA; urokinase-type plasminogen activator; z-VAD-fmk