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

Oncotarget. 2016 Apr 5;7(14):18763-73. doi: 10.18632/oncotarget.7708.

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.

Keywords: Fucus evanescens; TOPK; cell transformation; colon carcinoma; fucoidan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / drug effects
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / enzymology
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Epidermal Growth Factor / pharmacology*
  • Humans
  • Mice
  • Mice, Nude
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Phosphorylation
  • Polysaccharides / pharmacology*
  • Signal Transduction
  • Xenograft Model Antitumor Assays

Substances

  • Polysaccharides
  • Epidermal Growth Factor
  • fucoidan
  • Mitogen-Activated Protein Kinase Kinases
  • PDZ-binding kinase