Sensitization of chrysin on the apoptosis induced by cisplatin or camptothecin in hepatoma cell lines (Hep G2) / 中国药学杂志

ABSTRACT

OBJECTIVE: To investigate the effects of chrysin on the apoptosis induced by DNA damage antitumor drugs in hepatoma (Hep G2) cell lines, and its molecular mechanism. METHODS: Hep G2 cells were pretreated with chrysin for 2 h, then treated with cisplatin or camptothecin for 24 h. The morphologic changes were observed under inversed microscope and the cell viability was measured using MTT test. The proteins of caspase-3, PARP, Bcl-xL, xIAP and FLIP were determined by Western blot. RESULTS: Increases of cell death were observed in the combination of chrysin and cisplatin or camptothecin. There were significant differences in the cell viability not only between the combined treatment and the untreated control, but also between the combined treatment and chrysin alone, cisplatin alone or camptothecin alone. Chromatin condensation could be observed when the cells were stained by Hochest 33342 in the combination of chrysin and DNA damage antitumor drugs, and the apoptotic cells showed significant increase in the combination group compared with other groups(P < 0.05). The proproteins of caspase-3 and PARP degraded. The pan-caspase inhibitor z-VAD-fmk could inhibit the activation of caspase-3 and PARP induced by the combination of chrysin and cisplatin or camptothecin. The apoptosis inhibitory proteins, FLIP and xIAP which upregulated by cisplatin alone, could be downregulated by the cotreatment of chrysin and cisplatin; and Bcl-xL upregulated by camptothecin alone was downregulated by the combination of chrysin and camptothecin. CONCLUSION: Chrysin could sensitize the apoptosis induced by cisplatin and camptothecin, and the downregulation of apoptosis inhibitory proteins, which were regulated by NF-κB and augmented by cisplatin and camptothecin, played an important role in the sensitization.