Fig. 8. Schematic illustration of proposed mechanisms.

PPI inhibited proteasome function, and induced SQSTM1 elevated autophagy as a compensatory response for impaired proteasomal degradation. PPI promotes autophagic flux in neutral pH condition while blocks autophagic flux in low pH condition. When cancer cells were under proteins overload stress caused by proteasome inhibitors and autophagic flux blockers, or mitochondrial stress caused by Bcl-2 inhibitors, the cytotoxicity of PPI would be significantly increased