Abstract
Background: Lectins are carbohydrate-binding proteins that exhibit remarkable antitumor activities byinducing apoptotic or autophagic cell death. However, the relationship between apoptosis and autophagy induced bylectins has rarely been reported. Agrocybe aegerita lectin (AAL), a lectin isolated from the fungus Agrocybe aegerita,exerts antitumor activity through apoptosis.Objective: To study the relationship between the autophagy and apoptosis induced by AAL in hepatocellularcarcinoma (HCC) cells, and then to promote the antitumor effect of AAL.Method: AAL was evaluateted using the CCK-8 kit and the trypan blue assay. Cell autophagy was studied usingwestern blotting, acridine orange straining, transmission electron microscopy, and transient transfection of pEGFPLC3plasmids. We also evaluated AAL-induced autophagy in Caenorhabditis elegans. Apoptosis was studied usingflow cytometry. We also identified the antitumor effects of co-treatment of AAL with chloroquine (CQ) in vitro and invivo.Results: AAL-treated cell lines showed accumulation of microtubule-associated protein light chain 3 II (LC3-II),formation of EGFP-LC3 puncta and acidic autophagic vacuoles (AVOs), and the induction of autophagosomes.Inhibition of autophagy could enhance apoptosis induced by AAL in HCC cells. Furthermore, co-therapy (AAL andchloroquine) promote antitumor effect of AAL in a murine in situ HCC model.Conclusion: Our findings suggest that inhibition of autophagy exerts a synergistic effect on the antitumor activity ofAAL and may be a helpful strategy for reducing the dosage of lectin used in antitumor therapy. The autophagyinhibitor may be a synergist of certain antitumor drugs that can induce both apoptosis and autophagy.