Characterization and Inception of a Triterpenoid Astrakurkurol, as a Cytotoxic Molecule on Human Hepatocellular Carcinoma Cells, Hep3B.

Abstract

Mushrooms are customary influential sources of pharmaceutically active metabolites. Usually lanostane-type triterpenoids from mushrooms had prospective for cancer disease treatments. Recently, a triterpenoid, astrakurkurol obtained from the fresh basidiocarps of the edible mushroom Astraeus hygrometricus, drew attention as a new cytotoxic therapeutic. The structural stability of this triterpenoid had been established with the amalgamation of density functional theory (DFT) calculations and study of single-crystal X-ray diffraction. To successfully manifest astrakurkurol as a potent cytotoxic therapeutics, a wide apprehension on the molecular and cellular mechanisms underlying their action is prerequisite. On this account, our study was directed to scrutinize the influence of this triterpenoid on human hepatocellular cancer cell model Hep3B. Encapsulating all experimental facts revealed that astrakurkurol had significantly decreased cell viability in a concentration-dependent manner. This effect was unveiled to be apoptosis, documented by DNA fragmentation, chromatin condensation, nuclear shrinkage, membrane blebing, and imbalance of cell cycle distribution. Astrakurkurol persuaded the expression of death receptor associated proteins (Fas), which triggered caspase-8 activation following tBid cleavage. Moreover, tBid mediated ROS generation, which triggered mitochondrial dysfunction and activated the mitochondrial apoptotic events. Astrakurkurol cytotoxicity was based on caspase-8-mediated intrinsic apoptotic pathway and was associated with inhibition at Akt and NF-κB pathway. Astrakurkurol had also inhibited the migration of Hep3B cells, indicating its antimigratory potential. These findings led us to introduce astrakurkurol as a feasible and natural source for a safer cytotoxic drug against hepatocellular carcinoma.