Ergosterol peroxide from Pleurotus ferulae inhibits gastrointestinal tumor cell growth through induction of apoptosis via reactive oxygen species and endoplasmic reticulum stress.

Abstract

Ergosterol peroxide was purified from Pleurotus ferulae by silica gel chromatography, Sephadex LH-20 chromatography and recrystallization and named PFEP, which was identified by ESI-MS and NMR. PFEP significantly inhibited the proliferation of gastrointestinal tumor cells through induction of cell cycle arrest and apoptosis characterized by chromatin condensation and DNA fragmentation. Moreover, PFEP activated the mitochondria-dependent apoptosis pathway via increased ROS generation and Bax/Bcl-2 ratio, which decreased the mitochondrial membrane potential to promote cytochrome c release and the activation of caspases 3 and 9 to cleave poly (ADP-ribose) polymerase. Caspase inhibitors and ROS scavengers partially prevented apoptosis induced by PFEP. PFEP also induced endoplasmic reticulum stress characterized by the upregulated levels of p-PERK, p-eIF2α, ATF4 and CHOP. Importantly, PFEP suppressed tumor cell migration in vitro, inhibited CT26 tumor growth in vivo and improved the survival of tumor mice. PFEP might be a potential drug candidate for the treatment of gastrointestinal cancers.