4.6 Article

Dehydroeffusol effectively inhibits human gastric cancer cell-mediated vasculogenic mimicry with low toxicity

Journal

TOXICOLOGY AND APPLIED PHARMACOLOGY
Volume 287, Issue 2, Pages 98-110

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2015.05.003

Keywords

Gastric cancer; Dehydroeffusol; Vasculogenic mimicry; MMP2; VE-cadherin; Cancer neovascularization

Funding

  1. National Natural Science Foundation of China [81172087, 81372376]
  2. priority academic program development of Jiangsu Higher Education Institutions (PAPD)
  3. Research and Innovation Project for College Graduates of Jiangsu Province [CXZZ13_0824]
  4. Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Jiangsu Province's Key Discipline of Medicine [XK201118]
  5. Suzhou City Scientific Research Funds [SS201004, SS201138, SYS201418]
  6. Collaborative Innovation Center of Hematology, University

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Accumulated data has shown that various vasculogenic tumor cells, including gastric cancer cells, are able to directly form tumor blood vessels via vasculogenic mimicry, supplying oxygen and nutrients to tumors, and facilitating progression and metastasis of malignant tumors. Therefore, tumor vasculogenic mimicry is a rational target for developing novel anticancer therapeutics. However, effective antitumor vasculogenic mimicry-targeting drugs are not clinically available. In this study, we purified 2,7-dihydroxyl-1-methyl-5-vinyl-phenanthrene, termed dehydroeffusol, from the traditional Chinese medicinal herb Juncus effusus L, and found that dehydroeffusol effectively inhibited gastric cancer cell-mediated vasculogenic mimicry in vitro and in vivo with very low toxicity. Dehydroeffusol significantly suppressed gastric cancer cell adhesion, migration, and invasion. Molecular mechanistic studies revealed that dehydroeffusol markedly inhibited the expression of a vasculogenic mimicry master gene VE-cadherin and reduced adherent protein exposure on the cell surface by inhibiting gene promoter activity. In addition, dehydroeffusol significantly decreased the expression of a key vasculogenic gene matrix metalloproteinase 2 (MMP2) in gastric cancer cells, and diminished MMP2 protease activity. Together, our results showed that dehydroeffusol effectively inhibited gastric cancer cell-mediated vasculogenic mimicry with very low toxicity, suggesting that dehydroeffusol is a potential drug candidate for anti-gastric cancer neovascularization and anti-gastric cancer therapy. (C) 2015 Elsevier Inc. All rights reserved.

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