A polysaccharide from Lentinus edodes inhibits human colon cancer cell proliferation and suppresses tumor growth in athymic nude mice

Abstract

The antitumor effect of Lentinan is thought rely on the activation of immune responses; however, little is known about whether Lentinan also directly attacks cancer cells. We therefore investigated the direct antitumor activity of SLNT (a water-extracted polysaccharide from Lentinus edodes) and its probable mechanism. We showed that SLNT significantly inhibited proliferation of HT-29 colon cancer cells and suppressed tumor growth in nude mice. Annxein V-FITC/PI, DAPI, AO/EB and H&E staining assays all showed that SLNT induced cell apoptosis both in vitro and in vivo. SLNT induced apoptosis by activating Caspase-3 via both intrinsic and extrinsic pathways, which presented as the activation of Caspases-9 and -8, upregulation of cytochrome c and the Bax/Bcl-2 ratio, downregulation of NF-κB, and overproduction of ROS and TNF-α in vitro and in vivo. Pretreatment with the caspase-3 inhibitor Ac-DEVD-CHO or antioxidant NAC blocked SLNT-induced apoptosis. These findings suggest that SLNT exerts direct antitumor effects by inducing cell apoptosis via ROS-mediated intrinsic and TNF-α-mediated extrinsic pathways. SLNT may thus represent a useful candidate for colon cancer prevention and treatment.