Caspase-8 Activation

Hepatocellular carcinoma is a cancer of high mortality; therefore, the effective therapy on this cancer is an imperative issue. Recently, anticancer agent combined with natural products has been demonstrated to increase apoptosis of various cancer cells effectively. Accordingly, we investigated the apoptotic effect and possible mechanism of the ethanol extract from Taiwanofungus salmoneus (=Antrodia salmonea) mycelium (TsE) alone or in combination with cisplatin in SK-Hep-1 cells. In this study, the proliferation of SK-Hep-1 cells could be inhibited at various concentrations of TsE for 24 h whereas TsE combined with cisplatin would inhibit the cell proliferation more notably. Moreover, the DNA damage and the interruption of cell cycle of SK-Hep-1 cells would be effectively raised after incubation with TsE combined with cisplatin for 24 h. The apoptosis of cells was dramatically induced, and the expression of caspases 3, 8, and 9, apoptosis-related protein, were significantly upregulated. Therefore, we proposed that the TsE combined with cisplatin inhibited cell proliferation by elevating sub-G1 phase, inducing DNA damage, activating caspases 3, 8, and 9 activities, and triggering cells apoptosis. These results reveal that TsE could be a potential adjuvant chemotherapeutic agent.