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// 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 .

Accumulating data clearly indicate that the induction of apoptosis by nontoxic natural compounds is a potent defense against the development and progression of many malignancies, including colon cancer. Resveratrol and the fucoidans have been shown to possess potent anti-tumor activity in vitro and in vivo. The aim of the present study was to examine whether the combination of a fucoidan from the brown alga Saccharina cichorioides Miyabe and resveratrol would be an effective preventive and/or therapeutic strategy against colon cancer. Based on NMR spectroscopy and MALDI-TOF analysis, the fucoidan isolated and purified from Saccharina cichorioides Miyabe was (1→3)-α-l-fucan with sulfate groups at C2 and C4 of the α-l-fucopyranose residues. The fucoidan enhanced the antiproliferative activity of resveratrol at nontoxic doses and facilitated resveratrol-induced apoptosis in the HCT 116 human colon cancer cell line. Apoptosis was realized by the activation of initiator caspase-9 and effector caspase-7 and -3, followed by the cleavage of PARP. Furthermore, significant inhibition of HCT 116 colony formation was associated with the sensitization of cells to resveratrol by the fucoidan. Taken together, these results demonstrate that the combination of the algal fucoidan with resveratrol may provide a potential therapy against human colon cancer.