Figure 8

Scheme of PCD pathway in HCC cells triggered by TK VI. Ca²⁺ entered through the cell membrane and activated Bak and calpain. The former ignited autophagy characteristic of cytoplasmic vacuolation and the latter promoted the translocation of Bax, which targeted mitochondria. On the other hand, Bcl-xL was downregulated almost in concurrence with the translocation of Bax. Bcl-xL overexpression retarded apoptosis, whereas it had no effect on authoagy. The release of Cyto-c and Smac from mitochondria into the cytosol was triggered by the preceding events, promoting the acivation of caspase-3 which subsequently led to PARP activation. Specific depletion of Bak expression could partly attenuate TK VI-induced autophagy. However, blockage of Bax led to increased autophagy.