Sanggenon O induced apoptosis of A549 cells is counterbalanced by protective autophagy.

• It is the first time to characterize Sanggenon O as an anticancer compound. • Sanggenon O induced the expressions of cytoplasmic vacuoles and autophagic markers in NSCLC A549 cell line. • Sanggenon O suppressed autophagic flux in NSCLC A549 cell lines. • Sanggenon O induces cytoprotective autophagy in NSCLC A549 cell lines. Sanggenon O (SO) is a Diels-Alder type adduct extracted from Morus alba , which has been used for its anti-inflammatory action in the Oriental medicine. However, whether it has regulatory effect on human cancer cell proliferation and what the underlying mechanism remains unknown. Here, we found that SO could significantly inhibit the growth and proliferation of A549 cells and induce its pro-apoptotic action through a caspase-dependent pathway. It could also impair the mitochondria which can be reflected by mitochondrial membrane permeabilization. Besides, SQSTM1 up-regulation and autophagic flux measurement demonstrated that exposure to SO led to autophagosome accumulation, which plays a protective role in SO-treated cells. In addition, knocking down of LC3B increased SO triggered apoptotic cell rates. These results indicated that SO has great potential as a promising candidate combined with autophagy inhibitor for the treatment of NSCLC. In conclusion, our results identified a novel mechanism by which SO exerts potent anticancer activity. [ABSTRACT FROM AUTHOR]