title: 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.
authors.affiliation: Union Hospital of Huazhong University of Science and Technology, Department of Pharmacy, 430030, Wuhan, China.
authors.forename: Jinglin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Union Hospital of Huazhong University of Science and Technology, Department of Pharmacy, 430030, Wuhan, China.
authors.forename: Weiyong
authors.initials: W
authors.lastname: Li
authors.affiliation: Union Hospital of Huazhong University of Science and Technology, Department of Pharmacy, 430030, Wuhan, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Huang
authors.affiliation: Renmin Hospital of Wuhan University, Department of Pharmacy, 430060, Wuhan, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Union Hospital of Huazhong University of Science and Technology, Department of Pharmacy, 430030, Wuhan, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Union Hospital of Huazhong University of Science and Technology, Department of Pharmacy, 430030, Wuhan, China.
authors.forename: Ziming
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Hubei Key Laboratory of Nature Medicinal Chemistry and Resource Evaluation, Tongji Medical College of Pharmacy, Huazhong University of Science and Technology, 430030, Wuhan, China.
authors.forename: Kaiping
authors.initials: K
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D062610:Fungal Polysaccharides / Q000494:pharmacology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D017382:Reactive Oxygen Species; D020942:Shiitake Mushrooms / Q000737:chemistry*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D062610:Fungal Polysaccharides; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D053148:Caspase 3; D053453:Caspase 9
keywords: ROS; apoptosis; colon cancer; lentinan; nude mice