Isolation of an Exopolysaccharide From Inonotus hispidus Fermentation Broth and Its Antiproliferative Activity Against Hepatocellular Carcinoma Cell Line

ABSTRACT The antitumor activity of fungal polysaccharides has attracted considerable attention due to their high efficacy and low side effects. In this work, an extracellular polysaccharide fraction EPS‐3, exhibiting significant antiproliferative activity was obtained from Inonotus hispidus ( I. hispidus ) fermentation broth through an activity‐guided separation method. EPS‐3 was identified as an anionic, glucosyl‐branched mannoglucan polysaccharide composed of glucose, mannose, and glucuronic acid in the molar ratio of 1:0.19:0.04. It contains 1,4‐linked glucosyl and α ‐1,4/1,6‐linked mannosyl units and has a weight‐average molecular weight of 99 kDa. In HepG2 cancer cell culture, EPS‐3 reduced HepG2 cell viability by 51.68% at 300 µg/mL. EPS‐3 inhibited HepG2 cells proliferation by inducing apoptosis via cell cycle arrest through a mitochondria‐mediated caspase‐dependent pathway as evidenced by the excessive production of reactive oxygen species (ROS), the decrease in mitochondrial membrane potential and the elevated expression of apoptosis‐related proteins induced by EPS‐3 in HepG2 cells. Taken together, the I. hispidus ‐derived exopolysaccharide significantly contributes to the suppression of hepatic tumor cells and, therefore, may be further developed as a promising functional food component or an antitumor adjuvant for the prevention or treatment of liver cancer.