Silibinin Causes Upregulation of PTEN as One of the Cell Cycle Progression Blocker in MCF-7Human Breast Cancer Cell Line

Introduction: Silibinin, a natural flavonoid, has many anticancer effects including growth inhibition, cell cycle arrest, antiprolifrative effect and apoptosis induction while is well tolerated and largely free of any adverse effects. Methods: In the present study, we studied some of silibinin effects on MCF-7 cells. Cell viability was analyzed by MTT in silibinin treated cells. We investigated effect of silibinin on PTEN (phosphatase and tensin homolog) mRNA expression by Real-Time RT-PCR (Reverse transcription polymerase chain reaction) technique and cell cycle distribution by flow cytometry. Results: Findings of this study showed that silibinin induced dose-dependent cell death in MCF-7 cells. Silibinin induced PTEN overexpression and G1 cell cycle arrest. Discussion: These results suggest that PTEN overexpression has a role in anticancer mechanisms of silibinin in MCF-7 cells because of capacity of PTEN to evoke increases in the expression of the p27/Kip1, cyclin dependent kinase inhibitor via its lipid phosphatase and decreases in cyclin D via its protein phosphatase that predisposes cell cycle arrest and also PTEN leads to Bad activation that predisposes apoptotic cell death. Conclusion: Cell cycle arrest is one of the anti-cancer mechanisms of silibinin in MCF-7 cells that ismediated by modulation of some genes including PTEN.

Keywords:

Silibinin , Cell Cycle , PTEN