Compound of Stout Camphor Medicinal Mushroom, Taiwanofungus camphoratus (Agaricomycetes), Induces Protective Autophagy in SPCA-1 Cells through AMPK Inhibition-Independent Blockade of the Akt/mTOR Pathway

: Our previous study showed that By-1, a maleimide derivative isolated from Taiwanofungus camphoratus, could induce reactive oxygen species-triggered apoptosis and G2 cell cycle arrest through a caspase-dependent pathway and also induced protective autophagy in human lung cancer SPCA-1 cells. Here, we further examined the autophagy flux and detected related proteins by Western blot analysis and fluorescence activated cell sorting, and we sought to find the exact role and underlying pathway of autophagy in SPCA-1 cells. Our results showed that By-1 treatment activated autophagy flux in SPCA-1 cells, which further confirmed that autophagy was induced by By-1 treatment in our previous study. Autophagy activator rapamycin restored cell death from By-1 treatment (21.32%) and verified that autophagy played a protective role in By-l-treated cells. Meanwhile, By-1 treatment suppressed the Akt-mammalian target of rapamycin (mTOR) pathway and the AMP-activated protein kinase (AMPK) pathway. Taken together, these findings indicate that By-1 induced protective autophagy in SPCA-1 cells through AMPK inhibition-independent blockade of the Akt/mTOR pathway.