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

// Jinglin Wang 1 , Weiyong Li 1 , Xiao Huang 1 , Ying Liu 3 , Qiang Li 1 , Ziming Zheng 1 , Kaiping Wang 2 1 Union Hospital of Huazhong University of Science and Technology, Department of Pharmacy, 430030, Wuhan, China 2 Hubei Key Laboratory of Nature Medicinal Chemistry and Resource Evaluation, Tongji Medical College of Pharmacy, Huazhong University of Science and Technology, 430030, Wuhan, China 3 Renmin Hospital of Wuhan University, Department of Pharmacy, 430060, Wuhan, China Correspondence to: Kaiping Wang, email: wkpzcq@126.com Keywords: apoptosis, colon cancer, lentinan, nude mice, ROS Received: July 25, 2016      Accepted: November 14, 2016      Published: November 21, 2016 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.