Abstract

Hepatocellular carcinoma (HCC) is one of the most prevalent and deadliest cancers. In this study, the anti-tumor effect of singular degree of polymerization (DP) chitooligosaccharides (COS) (DP 2–5) and the underlay molecular mechanisms were investigated on HCC cell line HepG2. MTT assay showed that (GlcN) 5 have the best anti-proliferation effect among the different DP of COS (DP2-5). Furthermore, the administration of (GlcN) 5 could decrease mitochondrial membrane potential, release cytochrome c into cytoplasm, activate the cleavage of Caspases9/3, thus inducing mitochondrial-mediated apoptosis in HepG2 cells (accounting for 24.57 ± 2.25%). In addition, (GlcN) 5 treatment could increase the accumulation of autophagosomes. Further investigation showed that (GlcN) 5 suppressed protective autophagy at the fusion of autophagosomes and lysosomes. Moreover, the inhibition of protective autophagy flux by (GlcN) 5 could further decrease cell viability and increase the apoptosis rate. Our findings suggested that (GlcN) 5 suppressed HepG2 proliferation through inducing apoptosis via the intrinsic pathway and impairing cell-protective autophagy. COS might have the potential to be an agent for lowering the risk of HCC.