Wogonin and fisetin induction of apoptosis through activation of caspase 3 cascade and alternative expression of p21 protein in hepatocellular carcinoma cells SK-HEP-1.

摘要: Wogonin and fisetin are flavonoids, which widely distributed in plants. Our recent study demonstrated that, among seven structurally related wogonin showed the most potent apoptosis-inducing activities human promyeloleukemic cells HL-60. In present investigation, we performed molecular studies to assess apoptotic effects of on hepatocellular carcinoma SK-HEP-1. Both dose-dependent cytotoxic SK-HEP-1 cells, accompanied by DNA fragmentation. Microscopic observation under Giemsa staining that fisetin, at dose 80 µM, induced cellular swelling appearance bodies, characteristics apoptosis, cells. Furthermore, flow cytometry analysis an increase hypodiploid wogonin- fisetin-treated These data were effective inducers apoptosis Treatment with concentration or caused induction caspase 3/CPP32 activity, but not 1 activity. addition, a 3 inhibitor, Ac-DEVD-CHO, inhibitor Ac-YVAD-CHO, reversed Further, cleavage substrates including poly(ADP-ribose) polymerase (PARP) D4-GDI protein, decrease pro-caspase protein detected Increase p53 was associated fisetin-induced apoptosis; however, p53-controlled gene, p21Waf/Cip-1, only (not fisetin-) treated Serum starvation elevated p21Waf/Cip-1 expression, enhanced activity fiseitn) has provided evidence demonstrate had through SK-HEP-1; activation cascade, alternative expression involved.