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3229454 
Journal Article 
gamma-Oryzanol Reduces Caveolin-1 and PCGEM1 Expression, Markers of Aggressiveness in Prostate Cancer Cell Lines 
Hirsch, GE; Parisi, MM; Martins, LeoAM; Andrade, CMB; Barbe-Tuana, FM; Guma, FTCR 
2015 
1 
Prostate
ISSN: 0270-4137
EISSN: 1097-0045 
75 
8 
783-797 
WOS:000353235500001 
BACKGROUNDProstate cancer is a leading cause of death among men due to the limited number of treatment strategies available for advanced disease. -oryzanol is a component of rice bran, rich in phytosterols, known for its antioxidant, anti-carcinogenic and endocrinological effects. It is known that -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 -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).



METHODSTo determine the effects of -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.



RESULTSWe found that -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. -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.



CONCLUSIONIn summary, we used biochemical and genetics approaches to demonstrate that -oryzanol show a promising adjuvant role in the treatment of prostate cancer. Prostate 75:783-797, 2015. (c) 2015 Wiley Periodicals, Inc. 
-oryzanol; prostate cancer cell lines; survival genes; metastasis; androgen resistance