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Inhibitory effect of isoflavones on prostate cancer cells and PTEN gene
Feng Cao1, Tai-Yi Jin, Yuan-Fen Zhou
1Department of Occupational Health and Toxicology, School of Public Health, Fudan University, Shanghai 200032, China.
Objective:
To explore the mechanisms by which genistein and daidzein inhibit the growth of prostate cancer cells.
Methods:
LNCaP and PC-3 cells were exposed to genistein and daidzein and cell viability was determined by MTT assay and cytotoxicity of the drugs by LDH test. Flow cytometry (FCM) was used to assess the cell cycle in LNCaP and PC-3 cells. Reverse transcription-polymerase chain reaction (RT-PCR) was applied to examine the expression of PTEN gene (a tumor suppressor gene), estrogen receptor alpha gene (ERalpha), estrogen receptor beta gene (ERbeta), androgen receptor gene (AR) and vascular endothelial growth factor gene (VEGF).
Results:
The viability of PC-3 and LNCaP cells decreased with increasing concentrations and exposure time of genistein and daidzein. Genistein increased G2/M phase cells in PC-3 cells while decreased S phase cells in LNCaP cells in a dose-dependent manner. Daidzein exerted no influence on the cell cycle of LNCaP and PC-3 cells, but the apoptosis percentage of LNCaP cells was elevated significantly by daidzein. Genistein induced the expression of PTEN gene in PC-3 and LNCaP cells. Daidzein induced the expression of PTEN gene in LNCaP but not in PC-3 cells. The expression of VEGF, ERalpha and ERbeta genes decreased and AR gene was not expressed after incubation with genistein and daidzein in PC-3 cells. In LNCaP cells, the expression of VEGF and AR gene decreased but there was no change in the expression of ERalpha and ERbeta gene after incubation with genistein and daidzein. Conclusion Genistein and daidzein exert a time- and dose-dependent inhibitory effect on PC-3 and LNCaP cells. The down-regulation of ER gene by daidzein influences the growth of PC-3 cells directly. The inhibition of PC-3 cells by genistein and that of LNCaP cells by genistein and daidzein may be via Akt pathway that is repressed by PTEN gene, which subsequently down-regulates the expression of AR and VEGF genes. Our results suggest that the expression of PTEN gene plays a key role and several pathways may be involved in the suppression of prostate cancer cells by genistein and daidzein.
Insights
Genistein and daidzein inhibit prostate cancer cell growth in a dose-dependent manner. These compounds influence cell cycle, apoptosis, and gene expression, suggesting PTEN gene plays a key role in their anti-cancer effects.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Prostate cancer remains a significant health concern globally.
- Genistein and daidzein are soy isoflavones with potential anti-cancer properties.
- Understanding their mechanisms of action is crucial for therapeutic development.
Purpose of the Study:
- To investigate the inhibitory effects of genistein and daidzein on prostate cancer cell lines.
- To elucidate the molecular mechanisms underlying their anti-proliferative actions.
Main Methods:
- Prostate cancer cell lines (LNCaP and PC-3) were treated with genistein and daidzein.
- Cell viability assessed via MTT assay; cytotoxicity by LDH test.
- Cell cycle analysis performed using flow cytometry (FCM).
- Gene expression of PTEN, ERalpha, ERbeta, AR, and VEGF analyzed by RT-PCR.
Main Results:
- Genistein and daidzein reduced prostate cancer cell viability in a time- and dose-dependent manner.
- Genistein altered cell cycle progression (G2/M in PC-3, S in LNCaP).
- Daidzein increased apoptosis in LNCaP cells.
- Both compounds modulated PTEN, AR, and VEGF gene expression, with varying effects on ER genes.
Conclusions:
- Genistein and daidzein exhibit significant anti-prostate cancer cell activity.
- PTEN gene expression appears central to the inhibitory effects.
- Potential involvement of the Akt pathway and down-regulation of AR and VEGF.
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