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An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
γ-Oryzanol reduces caveolin-1 and PCGEM1 expression, markers of aggressiveness in prostate cancer cell lines
Gabriela E Hirsch1, Mariana M Parisi, Leo A M Martins
1Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil.
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.
Conclusion:
In summary, we used biochemical and genetics approaches to demonstrate that γ-oryzanol show a promising adjuvant role in the treatment of prostate cancer.
Insights
γ-oryzanol, a rice bran component, shows promise as an adjuvant prostate cancer treatment. It reduces cancer cell viability and biomass by inducing apoptosis and necrosis, while modulating key genes like caveolin-1 (Cav-1).
Area of Science:
- Oncology
- Biochemistry
- Molecular Biology
Background:
- Prostate cancer remains a leading cause of male mortality due to limited advanced treatment options.
- γ-oryzanol, a rice bran phytosterol, exhibits antioxidant, anti-carcinogenic, and endocrinological properties.
- γ-oryzanol components may influence prostate cancer progression by modulating genes such as caveolin-1 (Cav-1) and prostate specific androgen-regulated gene (PCGEM1).
Purpose of the Study:
- To investigate the effects of γ-oryzanol on prostate cancer cell survival and progression.
- To analyze the impact of γ-oryzanol on cell viability, death, cell cycle, and specific gene expression.
Main Methods:
- Cell viability and biomass assessed using MTT and sulforhodamine B assays.
- Cell death, cell cycle, and pERK1/2 activity analyzed via flow cytometry.
- Gene expression (Cav-1, PCGEM1) evaluated by RT-PCR; Cav-1 protein by immunofluorescence and confocal microscopy.
Main Results:
- γ-oryzanol decreased cell viability and biomass through apoptosis/necrosis in androgen-responsive and unresponsive prostate cancer cell lines.
- It modulated pERK1/2 signaling and cell cycle progression (G2/M or G0/G1 arrest).
- Downregulation of Cav-1 and PCGEM1 gene expression was observed in specific cell lines.
Conclusions:
- γ-oryzanol demonstrates potential as an adjuvant therapy for prostate cancer.
- Biochemical and genetic analyses support its promising role in prostate cancer treatment.
