Mushroom as new repository for small bioactive molecules for anticancer efficacy

Abstract

Approximately 270 species of mushrooms have been reported as potentially useful for human health. However, few mushrooms havebeen studied so far in treating various diseases. Like other natural regimens, the mushroom treatment appears safe, as could be expectedfrom their long culinary and medicinal use. At present, cancer is a leading cause of death worldwide. Nearly 10 million deaths wererecorded globally from different cancers in 2020. We have screened the anti-proliferative and apoptotic potentials of more than thirtyspecies of mushroom for their anticancer activity. The result reflects that a wild and edible mushroom, Astraeus hygrometricus, selectivelyinduces robust apoptosis in MOLT-4 cells by targeting the G0/G1 stage of the cell cycle. A unique triterpene, astrakurkurone, isolatedfrom this mushroom induces robust apoptosis by disrupting the mitochondrial membrane potential, augmenting reactive oxygenspecies (ROS) and RNS production. Induction of apoptosis is through activation of the intrinsic mitochondrial pathway by upregulatingBIM, a pro-apoptotic protein, and down-regulating XIAP, a survival protein. It also downregulates the phosphorylated AKT, which downregulatesphosphorylated FOXO and phosphorylated GSK3 β in the treated cells leading to apoptosis. Therefore, it can be envisagedthat mushroom-derived bioactive molecules will hold great promise in cancer treatment in the future.