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.