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.

Prospecting medicinal properties of Lion's mane mushroom

“…The pellet was fixed with chilled 70% (v/v) ethanol and stored at 4°C for at least 24 hr. Cells were then resuspended in PBS containing propidium iodide (PI; a concentration of 20 μg/ml) and RNaseA (a concentration of 20 μg/ml) to stain DNA for 15 min (Nandi et al., 2019). Cells were then subjected to flow cytometer (BD accuri c6 plus, San Diego, CA), and the fraction of cells at each cell cycle was quantified with BD FACS Suite software.…”

Functional foods’ bioactive components and their chemoprevention mechanism in cervical, breast, and liver cancers: A systematic review

“…Astrakurkurol, a triterpenoid extracted from fresh basidiocarps of the edible mushroom Astraeus hygrometricus was found to have anti-proliferative properties [50]. Astraeus hygrometricus has various health benefits such as anticancer, antidiabetic, and antioxidant properties [107][108].…”

“…Astraeus hygrometricus has various health benefits such as anticancer, antidiabetic, and antioxidant properties [107][108]. Nandi and colleagues [50] demonstrated that astrakurkurol can act as a cytotoxic drug. It was found to induce apoptosis in hepatocarcinoma cell line (Hep3B) and arrest cell cycle at the G0/G1 phase.…”

A natural derivative from ethnomedicinal mushroom potentiates apoptosis, autophagy and attenuates cell migration, via fine tuning the Akt signaling in human lung adenocarcinoma cells (A549)

“…A549 cells were grown 85%–90% confluency in a 6‐well plate and scratch assay was carried out according to our previous description 20 . Samples were treated with different concentrations (0, 10.3, 20.6, and 30.9 μM) of astrakurkurol.…”

“…The helical structure of astrakurkurol ignites further interest into the role of helicity in anticancer activity. Moreover, concerning the anticancer efficacy of astrakurkurol, its part in the induction of apoptosis has been previously reported in liver cancer cells 20 . In our present study, we have tried to inspect the effect of astrakurkurol on apoptosis and/or autophagy and metastasis in lung adenocarcinoma (A549) cells, as the effect of autophagy and apoptosis has never been tested upon it so far with astrakurkurol.…”