2. Academic Validation
  3. Dehydroeffusol effectively inhibits human gastric cancer cell-mediated vasculogenic mimicry with low toxicity

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

  • Toxicol Appl Pharmacol. 2015 Sep 1;287(2):98-110. doi: 10.1016/j.taap.2015.05.003.
Wenming Liu 1,  Mei Meng 1,  Bin Zhang 1,  Longsheng Du 1,  Yanyan Pan 1,  Ping Yang 1,  Zhenlun Gu 1,  Quansheng Zhou 2,  Zhifei Cao 3
Affiliations

Affiliations

  • 1 Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, University, 2011 Collaborative Innovation Center of Hematology, Suzhou, Jiangsu 215123, PR China; The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215123, PR China; Suzhou Institute of Chinese Materia Medica, Suzhou, Jiangsu 215123, PR China; Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, Jiangsu 215123, PR China; Soochow University, Suzhou, Jiangsu 215123, PR China.
  • 2 Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, University, 2011 Collaborative Innovation Center of Hematology, Suzhou, Jiangsu 215123, PR China; The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215123, PR China; Suzhou Institute of Chinese Materia Medica, Suzhou, Jiangsu 215123, PR China; Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, Jiangsu 215123, PR China; Soochow University, Suzhou, Jiangsu 215123, PR China. Electronic address: quanshengzhou@yahoo.com.
  • 3 Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, University, 2011 Collaborative Innovation Center of Hematology, Suzhou, Jiangsu 215123, PR China; The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215123, PR China; Suzhou Institute of Chinese Materia Medica, Suzhou, Jiangsu 215123, PR China; Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou, Jiangsu 215123, PR China; Soochow University, Suzhou, Jiangsu 215123, PR China. Electronic address: hunancao@163.com.
PMID: 25982451 DOI: 10.1016/j.taap.2015.05.003
Abstract

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.

Keywords

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

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