Formosanin C induces autophagy-mediated cell death in hepatocellular carcinoma through activating DUSP1/AMPK/ULK1/Beclin1 signaling pathway.

BACKGROUND

Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers and is associated with poor survival. Formosanin C (FC) is a diosgenin glycoside extracted from Paris polyphylla. Therapeutic effects of FC against HCC malignancies remain unclear.

PURPOSE

This study aimed to understand the anti-HCC effects of FC and to disclose the underlying mechanisms.

STUDY DESIGN

We evaluated the effects of FC on HCC malignancies by using two HCC cell lines, HepG2 and Huh-7, and a xenograft model.

METHODS

Multiple assessment methods were used, including CCK-8, colony formation, flow cytometry, wound healing, transwell and Western blot. Bioinformatic analyses such as network pharmacology were also employed. Xenograft mouse model was used to evaluate in vivo efficacy.

RESULTS

FC treatment remarkedly suppressed HepG2 and Huh-7 cell proliferation, migration and invasion, and induced cell apoptosis. Such anti-HCC effects of FC mainly attributed to the upregulation of DUSP1 expression and the subsequent activation of autophagy via AMPK/ULK1/Beclin1 axis. Inhibition of autophagy weakened the therapeutic effects of FC. Xenograft model analysis provided in vivo evidence that FC suppressed HCC tumor growth via DUSP1.

CONCLUSIONS

FC is therapeutically effective to suppress HCC malignancies principally via activation of the DUSP1/AMPK/ULK1/Beclin1-mediated autophagy. Our findings provide a novel promising drug candidate for treating HCC.