title: Dehydroeffusol effectively inhibits human gastric cancer cell-mediated vasculogenic mimicry with low toxicity.
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.
authors.affiliation: 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.
authors.forename: Wenming
authors.initials: W
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Mei
authors.initials: M
authors.lastname: Meng
authors.affiliation: 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.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Longsheng
authors.initials: L
authors.lastname: Du
authors.affiliation: 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.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Pan
authors.affiliation: 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.
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Zhenlun
authors.initials: Z
authors.lastname: Gu
authors.affiliation: 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.
authors.forename: Quansheng
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: Zhifei
authors.initials: Z
authors.lastname: Cao
mesh_terms: D015703:Antigens, CD; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015820:Cadherins / Q000037:antagonists & inhibitors; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010616:Phenanthrenes / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000188:drug therapy*; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D000970:Antineoplastic Agents; D015820:Cadherins; D004365:Drugs, Chinese Herbal; D020778:Matrix Metalloproteinase 2; D010616:Phenanthrenes; D000099152:Cadherin 5; C573784:dehydroeffusol
keywords: Cancer neovascularization; Dehydroeffusol; Gastric cancer; MMP2; VE-cadherin; Vasculogenic mimicry