Studies On The Inhibitory Mechanisms Of Silibinin In UV Irradiation-induced Cell Apoptosis

The mechanism of silibinin against UV irradiation in vitro was studied in this dissertation. Anti-apoptotic effects of silibinin on UV-irradiated human malignant melanoma cell A375-S2 and human keratinocyte cell HaCaT, were demonstrated, in addition, the effect of silibinin on anti-Fas agonistic antibody CH11-treated cells was investigated.In recent years, accumulating evidence has strongly suggested that dysregulation of apoptosis is the major cause of various diseases. It was first found in our study that silibinin, a plant flavonoid from seeds and fruits of milk thistle (Silybum marianum [L] Gaertner) had protective effect against UV irradiation-induced apoptosis, especially in A375-S2 cells and HaCaT cells.As the results show, 1) Anti-apoptotic effect of silibinin against UV in A375-S2 cells is exerted by activation of Akt, MAPK and SIRT1 pathways, as well as blockage of signal transduction of mitochondrial and caspase pathways. It was also found that silibinin has positive effect on distribution of A375-S2 cell cycle. Pre-treatment with silibinin reversed the UV-induced S arrest, resulting in an increase in G₂/M phase cells, which allowed cells more time to repair damaged DNA before mitosis (M phase). In addition, silibinin did not show the effect on the activity of telomerase which could directly regulate the life-span of cells. 2) UV-induced HaCaT cell apoptosis was significantly reversed by silibinin pretreatment which was partially mediated by inhibition of caspase-8 pathway after reduction of FADD's expression.Binding of death ligand such as FasL, or agonistic antibodies to their cognate receptors induces apoptosis. In the study of the effect of silibinin on the cytotoxity of anti-Fas agonistic antibody CH11, it was found that silibinin could exaggerate the apoptotic effect of anti-Fas agonistic antibody CH11 on A375-S2 cells via activation of caspases, CD95 (Fas/APO-1) and post-mitochondrial pathways.In conclusion, the present results show that silibinin appears to the effect of protecting...