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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

2016; Impact Journals LLC; Volume: 7; Issue: 14 Linguagem: Inglês

10.18632/oncotarget.7708

1949-2553

Olesia S. Vishchuk, Huimin Sun, Zhe Wang, Svetlana P. Ermakova, Juanjuan Xiao, Tao Lu, Peipei Xue, T. N. Zvyagintseva, Hua Xiong, Chen Shao, Wei Yan, Qiuhong Duan, Feng Zhu,

Bioactive Compounds and Antitumor Agents

// Olesia S. Vishchuk 1, 2, * , Huimin Sun 3, * , Zhe Wang 4 , Svetlana P. Ermakova 2 , JuanJuan Xiao 1 , Tao Lu 1 , PeiPei Xue 1 , Tatyana N. Zvyagintseva 2 , Hua Xiong 1 , Chen Shao 3, 5 , Wei Yan 4 , Qiuhong Duan 1 , Feng Zhu 1 1 Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China 2 G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of Russian Academy of Sciences, Laboratory of Enzyme Chemistry, 690022 Vladivostok, Russian Federation 3 Department of Urology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, PR China 4 Department of Pathology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, PR China 5 State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi 710032, PR China * These authors have contributed equally to this work Correspondence to: Wei Yan, e-mail: yanwei@fmmu.edu.cn Qiuhong Duan, e-mail: duanqhwz@hust.edu.cn Feng Zhu, e-mail: fengzhu@hust.edu.cn Keywords: fucoidan, Fucus evanescens , TOPK, cell transformation, colon carcinoma Received: November 01, 2015 Accepted: January 29, 2016 Published: February 25, 2016 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 .