title: The dietary bioflavonoid, quercetin, selectively induces apoptosis of prostate cancer cells by down-regulating the expression of heat shock protein 90.
abstract: BACKGROUND
  Human and animal studies have suggested that diet-derived flavonoids, in particular quercetin may play a beneficial role by preventing or inhibiting oncogenesis, but the underlying mechanism remains unclear. The aim of this study is to evaluate the effect(s) of quercetin on normal and malignant prostate cells and to identify the target(s) of quercetin's action.
  
  
  METHODS
  We addressed this question using cells in culture and investigated whether quercetin affects key biological processes responsible for tumor cell properties such as cell proliferation and apoptosis and also studied the effect of quercetin on the proteome of prostate cancer cells using difference gel electrophoresis (DIGE) to assess changes in the expression of relevant proteins.
  
  
  RESULTS
  Our findings demonstrate that quercetin treatment of prostate cancer cells results in decreased cell proliferation and viability. Furthermore, we demonstrate that quercetin promotes cancer cell apoptosis by down-regulating the levels of heat shock protein (Hsp) 90. Depletion of Hsp90 by quercetin results in decreased cell viability, levels of surrogate markers of Hsp90 inhibition (intracellular and secreted), induced apoptosis and activation of caspases in cancer cells but not in normal prostate epithelial cells. Knockdown of Hsp90 by short interfering RNA also resulted in induction apoptosis similar to quercetin in cancer cells as indicated by annexin V staining.
  
  
  CONCLUSIONS
  Our results demonstrate that quercetin down-regulates the expression of Hsp90 which, in turn, induces inhibition of growth and cell death in prostate cancer cells while exerting no quantifiable effect on normal prostate epithelial cells.
authors: Division of Allergy, Immunology and Rheumatology, Department of Medicine, State University of New York at Buffalo, Buffalo General Hospital, Kaleida Health, Buffalo, New York, USA.
authors: Ravikumar
authors: R
authors: Aalinkeel
authors: B
authors: B
authors: Bindukumar
authors: Jessica L
authors: JL
authors: Reynolds
authors: Donald E
authors: DE
authors: Sykes
authors: Supriya D
authors: SD
authors: Mahajan
authors: Kailash C
authors: KC
authors: Chadha
authors: Stanley A
authors: SA
authors: Schwartz
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017304:Annexin A5 / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects*; D005419:Flavonoids / Q000494:pharmacology; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D040901:Proteomics; D011794:Quercetin / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection
chemical_list: D017304:Annexin A5; D000975:Antioxidants; D005419:Flavonoids; D018841:HSP90 Heat-Shock Proteins; D018971:Insulin-Like Growth Factor Binding Protein 2; D034741:RNA, Small Interfering; D011794:Quercetin; D053148:Caspase 3; D053453:Caspase 9