title: γ-Oryzanol reduces caveolin-1 and PCGEM1 expression, markers of aggressiveness in prostate cancer cell lines.
abstract: BACKGROUND
  Prostate cancer is a leading cause of death among men due to the limited number of treatment strategies available for advanced disease. γ-oryzanol is a component of rice bran, rich in phytosterols, known for its antioxidant, anti-carcinogenic and endocrinological effects. It is known that γ-oryzanol may affect prostate cancer cells through the down regulation of the antioxidant genes and that phytosterols have anti-proliferative and apoptotic effects. There are evidences showing that some of the components of γ-oryzanol can modulate genes involved in the development and progression of prostate cancer, as caveolin-1 (Cav-1) and prostate specific androgen-regulated gene (PCGEM1).
  
  
  METHODS
  To determine the effects of γ-oryzanol on prostate cancer cell survival we evaluated the cell viability and biomass by MTT and sulforhodamine B assays, respectively. Cell death, cell cycle and pERK1/2 activity were assessed by flow cytometry. The changes in gene expression involved in the survival and progression of prostate cancer cav-1 and PCGEM1 genes were evaluated by quantitative real time reverse transcriptase polymerase chain reaction (RT-PCR) and cav-1 protein by immunofluorescence followed by confocal microscopy analysis.
  
  
  RESULTS
  We found that γ-oryzanol decreases cell viability and culture biomass by apoptosis and/or necrosis death in androgen unresponsive (PC3 and DU145) and responsive (LNCaP) cell lines, and signals through pERK1/2 in LNCaP and DU145 cells. γ-oryzanol also appears to block cell cycle progression at the G2/M in PC3 and LNCaP cells and at G0/G1 in DU145 cells. These effects were accompanied by a down regulation in the expression of the cav-1 in both androgen unresponsive cell lines and PCGEM1 gene in DU145 and LNCaP cells.
  
  
  CONCLUSIONS
  In summary, we used biochemical and genetics approaches to demonstrate that γ-oryzanol show a promising adjuvant role in the treatment of prostate cancer.
authors.affiliation: Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil.
authors.forename: Gabriela E
authors.initials: GE
authors.lastname: Hirsch
authors.forename: Mariana M
authors.initials: MM
authors.lastname: Parisi
authors.forename: Leo A M
authors.initials: LA
authors.lastname: Martins
authors.forename: Claudia M B
authors.initials: CM
authors.lastname: Andrade
authors.forename: Florencia M
authors.initials: FM
authors.lastname: Barbé-Tuana
authors.forename: Fátima T C R
authors.initials: FT
authors.lastname: Guma
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D051242:Caveolin 1 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D010666:Phenylpropionates / Q000494:pharmacology* / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*
chemical_list: C495540:CAV1 protein, human; D051242:Caveolin 1; C416084:PCGEM1 non-coding RNA, human; D010666:Phenylpropionates; D062085:RNA, Long Noncoding; C013172:gamma-oryzanol
keywords: androgen resistance; metastasis; prostate cancer cell lines; survival genes; γ-oryzanol