A recent study, published online in Redox Biology, revealed a new antitumour mechanism of yeast β-glucan in liver cancer. Performed by a team led by Prof. YIN Huiyong from Shanghai Institute of Nutrition and Health (SINH) of the Chinese Academy of Sciences and the collaborators, it discovered that water-soluble yeast β-glucan (WSG) is a novel autophagy inhibitor with significant antitumour efficacy through impairing autophagy and lysosomal function, promoting reactive oxygen species production and apoptosis.

As the most common primary liver cancer, hepatocellular carcinoma (HCC) ranks as the fourth leading cause of cancer deaths worldwide. Autophagy is an evolutionarily conserved catabolic process that can be induced under nutrient deprivation, hypoxia and diverse cellular stresses. The role of autophagy in the initiation and development of HCC remains poorly defined. Understanding the molecular mechanisms of autophagy at different stages of HCC may help to provide therapeutic targets for HCC treatment.

β-D-glucan is a polysaccharide composed of D-glucose monomers and is naturally found in bacteria, fungi, algae and cereal. Diverse biological effects of β-D-glucan have been reported, such as immune enhancement, antitumour, antioxidant and anti-hypertension.

In this study, the researchers discovered that WSG exerts significant antitumour efficacy on the inhibition of HCC cells proliferation and metabolism as well as the tumour growth in vivo. Mechanistically, WSG inhibits autophagic degradation by increasing lysosomal pH and inhibiting lysosome Cathepsins (Cathepsin B and D) activities, which results in the accumulation of damaged mitochondria and reactive oxygen species (ROS).

Furthermore, they found that WSG sensitizes HCC cells to apoptosis via the activation of caspase 8 and the transfer of truncated BID (tBID) into mitochondria under nutrient deprivation condition. Of note, administration of WSG as a single agent achieves a significant antitumour effect in a xenograft mouse model and DEN/CCl₄ (diethylnitrosamine/carbon tetrachloride)-induced primary HCC model without apparent toxicity.

This study reveals, for the first time, that WSG is a novel autophagy inhibitor with significant antitumour efficacy as a single agent, which has great potential in clinical application for liver cancer therapy.

A working model of antitumour effect of WSG by inhibiting autophagic degradation. (Image by Prof. YIN Huiyong's team)