title: PDZ-binding kinase/T-LAK cell-originated protein kinase is a target of the fucoidan from brown alga Fucus evanescens in the prevention of EGF-induced neoplastic cell transformation and colon cancer growth.
abstract: The fucoidan with high anticancer activity was isolated from brown alga Fucus evanescens. The compound effectively prevented EGF-induced neoplastic cell transformation through inhibition of TOPK/ERK1/2/MSK 1 signaling axis. In vitro studies showed that the fucoidan attenuated mitogen-activated protein kinases downstream signaling in a colon cancer cells with different expression level of TOPK, resulting in growth inhibition. The fucoidan exerts its effects by directly interacting with TOPK kinase in vitro and ex vivo and inhibits its kinase activity. In xenograft animal model, oral administration of the fucoidan suppressed HCT 116 colon tumor growth. The phosphorylation of TOPK downstream signaling molecules in tumor tissues was also inhibited by the fucoidan. Taken together, our findings support the cancer preventive efficacy of the fucoidan through its targeting of TOPK for the prevention of neoplastic cell transformation and progression of colon carcinomas in vitro and ex vivo.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China.|G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of Russian Academy of Sciences, Laboratory of Enzyme Chemistry, 690022 Vladivostok, Russian Federation.
authors.forename: Olesia S
authors.initials: OS
authors.lastname: Vishchuk
authors.affiliation: Department of Urology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, PR China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Pathology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, PR China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of Russian Academy of Sciences, Laboratory of Enzyme Chemistry, 690022 Vladivostok, Russian Federation.
authors.forename: Svetlana P
authors.initials: SP
authors.lastname: Ermakova
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China.
authors.forename: JuanJuan
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Lu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China.
authors.forename: PeiPei
authors.initials: P
authors.lastname: Xue
authors.affiliation: G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of Russian Academy of Sciences, Laboratory of Enzyme Chemistry, 690022 Vladivostok, Russian Federation.
authors.forename: Tatyana N
authors.initials: TN
authors.lastname: Zvyagintseva
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: Xiong
authors.affiliation: Department of Urology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, PR China.|State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi 710032, PR China.
authors.forename: Chen
authors.initials: C
authors.lastname: Shao
authors.affiliation: Department of Pathology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China.
authors.forename: Qiuhong
authors.initials: Q
authors.lastname: Duan
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010766:Phosphorylation; D011134:Polysaccharides / Q000494:pharmacology*; D015398:Signal Transduction; D023041:Xenograft Model Antitumor Assays
chemical_list: D011134:Polysaccharides; D004815:Epidermal Growth Factor; C007789:fucoidan; D020929:Mitogen-Activated Protein Kinase Kinases; C409022:PDZ-binding kinase
keywords: Fucus evanescens; TOPK; cell transformation; colon carcinoma; fucoidan