Cell cycle arrest of silibinin

2012-11-07 classification: efficacy 0 people commented that an important mechanism of tumor development is uncontrolled growth caused by abnormal cell cycle Therefore, it is an effective anti-cancer way to intervene the cell cycle process and then inhibit its proliferation CDK4 (Cdk6) / cyclin D1 and CDK2 / cyclin E play an important role in G1 / S phase progression and GL / S phase transition Zix et al Found that silybin (sb) can cause G1 phase arrest, s, G2 / M phase proportion decrease, cell growth is significantly inhibited The activity of CDK4 / cdk6-cyclin Di and cdk2-cyclin e-kinase decreased significantly in the aspect of kinase activity, but in the aspect of protein expression level, CDK4 and Cdk6 protein decreased moderately, cyclin D1 decreased or even disappeared significantly, while CDK2 and cyclin E level did not change Cyclin dependent protein kinase inhibitors (CKI) p2l and p27 can inhibit their activities by binding to CDK cyclin complex The results showed that silybin (sb) could up regulate the expression of p21 and P2, increase its binding with CDK2, and further inhibit the activity of CDK2 Agarwal C et al Found that silybin (sb) at low concentration (50-75 μ g / ml) could cause G1 phase arrest and S phase proportion decrease in colon cancer HT-29 cells, accompanied by CDK2, CDK4, decreased levels of cyclin D1, cyclin E and decreased activities of CDK2 and CDK4 kinase, while p21 and p27 protein levels increased significantly Sharma g et al Found that s could cause G1 phase arrest of shp-77 and A-549 cells, with growth inhibition and time-dose-dependent apoptosis Retinoblastoma gene (Rb gene) is a kind of tumor suppressor gene RB can inhibit the activity of transcription factor E2F in dephosphorylation state and make the cell stagnate in G1 phase After phosphorylation, Rb released transcription factors to activate its downstream genes, which made the cells enter S phase In dephosphorylation, Rb can cause g, phase arrest Tyagi a et al Reported that silybin (sb) could significantly increase the dephosphorylation level of Rb / p107, Rb2 / pl30 in prostate cancer DU145 cells, and the levels of transcription factors E2F3, E2F5 and CDK4, CDK2 protein were significantly reduced, while p21 and p27 were significantly increased, and G1 phase was strongly blocked Tyagia et al also observed that silybin (sb) could increase the level of total Rb protein, which was mainly dephosphorylated Rb, and the binding of Rb with MR, EM, E2F3 was significantly increased, EM, E2F3, CDK2, CDK4, cyclin D1 were significantly decreased, G1 phase was significantly blocked The activation of CDC 34 and cyclin B1 is the key molecule of cell from G2 to M phase, in which weel, CHK1 and CHK2 have a negative regulatory effect and cdc25c has a positive effect Agarwal C et al Found that silybin (sb) at high concentration (l00gg / ml) could cause G1 and G2 / m double phase arrest of HT-29 cells, accompanied by the downregulation of CDC2 / p34, cyclin Bi protein level and the downregulation of CDC2 / p34 kinase activity, but had no effect on the protein levels of weel, Chkl and CHK2 Tyagi a et al also found that silybin (sb) can cause Bi phase arrest of GI, G2 / m in tcc-sup cells, accompanied by decreased levels and activities of p21, p27, cdc25c, cdc2 proteins, and decreased levels of cyclin BL