[gamma]-oryzanol reduces caveolin-1 and PCGEM1 expression, markers of aggressiveness in prostate cancer cell lines

BACKGROUND Prostate cancer is a leading cause of death among men due to the limited number of treatment strategies available for advanced disease. [gamma]-oryzanol is a component of rice bran, rich in phytosterols, known for its antioxidant, anti-carcinogenic and endocrinological effects. It is know...

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Published in:The Prostate 2015-06, Vol.75 (8), p.783
Main Authors: Hirsch, Gabriela E, Parisi, Mariana M, Martins, Leo AM, Andrade, Claudia MB, Barbe-Tuana, Florencia M, Guma, Fátima TCR
Format: Article
Language:English
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Summary:BACKGROUND Prostate cancer is a leading cause of death among men due to the limited number of treatment strategies available for advanced disease. [gamma]-oryzanol is a component of rice bran, rich in phytosterols, known for its antioxidant, anti-carcinogenic and endocrinological effects. It is known that [gamma]-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 [gamma]-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 [gamma]-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 [gamma]-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. [gamma]-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. CONCLUSION In summary, we used biochemical and genetics approaches to demonstrate that [gamma]-oryzanol show a promising adjuvant role in the treatment of prostate cancer. Prostate 75:783-797, 2015. © 2015 Wiley Periodicals, Inc.
ISSN:0270-4137
1097-0045
DOI:10.1002/pros.22960