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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. - Highlights: •more » Dehydroeffusol markedly inhibits gastric cancer cell-mediated vasculogenic mimicry. • Dehydroeffusol suppresses the expression of vasculogenic mimicry key gene VE-cadherin. • Dehydroeffusol decreases the MMP2 expression and activity in gastric cancer cells. • Dehydroeffusol is a potential anti-cancer drug candidate with very low toxicity.« less

Authors:
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Publication Date:
OSTI Identifier:
22465810
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 287; Journal Issue: 2; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ADHESION; AVAILABILITY; BLOOD VESSELS; DRUGS; GENES; GROWTH FACTORS; HERBS; HUMAN POPULATIONS; IN VITRO; IN VIVO; METASTASES; NEOPLASMS; NUTRIENTS; PHENANTHRENE; RECEPTORS; THERAPY; TOXICITY; TUMOR CELLS

Citation Formats

Liu, Wenming, Meng, Mei, Zhang, Bin, Du, Longsheng, Pan, Yanyan, Yang, Ping, Gu, Zhenlun, Zhou, Quansheng, E-mail: quanshengzhou@yahoo.com, and Cao, Zhifei, E-mail: hunancao@163.com. Dehydroeffusol effectively inhibits human gastric cancer cell-mediated vasculogenic mimicry with low toxicity. United States: N. p., 2015. Web. doi:10.1016/J.TAAP.2015.05.003.
Liu, Wenming, Meng, Mei, Zhang, Bin, Du, Longsheng, Pan, Yanyan, Yang, Ping, Gu, Zhenlun, Zhou, Quansheng, E-mail: quanshengzhou@yahoo.com, & Cao, Zhifei, E-mail: hunancao@163.com. Dehydroeffusol effectively inhibits human gastric cancer cell-mediated vasculogenic mimicry with low toxicity. United States. doi:10.1016/J.TAAP.2015.05.003.
Liu, Wenming, Meng, Mei, Zhang, Bin, Du, Longsheng, Pan, Yanyan, Yang, Ping, Gu, Zhenlun, Zhou, Quansheng, E-mail: quanshengzhou@yahoo.com, and Cao, Zhifei, E-mail: hunancao@163.com. Tue . "Dehydroeffusol effectively inhibits human gastric cancer cell-mediated vasculogenic mimicry with low toxicity". United States. doi:10.1016/J.TAAP.2015.05.003.
@article{osti_22465810,
title = {Dehydroeffusol effectively inhibits human gastric cancer cell-mediated vasculogenic mimicry with low toxicity},
author = {Liu, Wenming and Meng, Mei and Zhang, Bin and Du, Longsheng and Pan, Yanyan and Yang, Ping and Gu, Zhenlun and Zhou, Quansheng, E-mail: quanshengzhou@yahoo.com and Cao, Zhifei, E-mail: hunancao@163.com},
abstractNote = {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. - Highlights: • Dehydroeffusol markedly inhibits gastric cancer cell-mediated vasculogenic mimicry. • Dehydroeffusol suppresses the expression of vasculogenic mimicry key gene VE-cadherin. • Dehydroeffusol decreases the MMP2 expression and activity in gastric cancer cells. • Dehydroeffusol is a potential anti-cancer drug candidate with very low toxicity.},
doi = {10.1016/J.TAAP.2015.05.003},
journal = {Toxicology and Applied Pharmacology},
number = 2,
volume = 287,
place = {United States},
year = {Tue Sep 01 00:00:00 EDT 2015},
month = {Tue Sep 01 00:00:00 EDT 2015}
}
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