Chitopentaose inhibits hepatocellular carcinoma by inducing mitochondrial mediated apoptosis and suppressing protective autophagy

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.

Keywords

Chitooligosaccharides / Singular DP / HCC / Apoptosis / Autophagy

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Funding

“Shu Guang” project of Shanghai Municipal Education Commission and Shanghai Education Development Foundation(15SG28)

China Postdoctoral Science Foundation(2017M621392)

Fundamental Research Funds for the Central Universities(22221818014)

Open Project Funding of the State Key Laboratory of Bioreactor Engineering, ECUST(ZDXM2019)

Shanghai PuJiang Program(18PJ1401900)