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Molecular Pharmacology

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Research ArticleOriginal Article

Pseudolarix Acid B, a New Tubulin-Binding Agent, Inhibits Angiogenesis by Interacting with a Novel Binding Site on Tubulin

Yun-Guang Tong, Xiong-Wen Zhang, Mei-Yu Geng, Jian-Ming Yue, Xian-Liang Xin, Fang Tian, Xu Shen, Lin-Jiang Tong, Mei-Hong Li, Chao Zhang, Wei-Hong Li, Li-Ping Lin and Jian Ding
Molecular Pharmacology April 2006, 69 (4) 1226-1233; DOI: https://doi.org/10.1124/mol.105.020537
Yun-Guang Tong
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Xiong-Wen Zhang
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Mei-Yu Geng
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Jian-Ming Yue
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Xian-Liang Xin
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Fang Tian
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Xu Shen
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Lin-Jiang Tong
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Mei-Hong Li
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Chao Zhang
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Wei-Hong Li
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Li-Ping Lin
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Jian Ding
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Abstract

Tubulin-binding agents have received considerable interest as potential tumor-selective angiogenesis-targeting drugs. Herein, we report that pseudolarix acid B (PAB), isolated from the traditional Chinese medicinal plant Pseudolarix kaempferi Gordon, is a tubulin-binding agent. We further demonstrate that PAB significantly and dose-dependently inhibits proliferation, migration, and tube formation by human microvessel enthothelial cells. It is noteworthy that PAB eliminated newly formed endothelial tubes and microvessels both in vitro and in vivo. In addition, PAB dramatically arrested the cell cycle at G2/M phase. PAB also induced endothelial cell retraction, intercellular gap formation, and promoted actin stress fiber formation in conjunction with disruption of the tubulin and actin cytoskeletons. All of these effects occurred at noncytotoxic concentrations of PAB. We found that these effects of PAB are attributable to depolymerization of tubulin by direct interaction with a distinct binding site on tubulin compared with those of colchicine and vinblastine. Taken together, these findings show that PAB is a candidate antiangiogenic agent for use in cancer therapy, and they provide proof of principle for targeting this novel binding site on tubulin as a new strategy for treating cancer.

  • Received November 6, 2005.
  • Accepted January 19, 2006.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 69 (4)
Molecular Pharmacology
Vol. 69, Issue 4
1 Apr 2006
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Research ArticleOriginal Article

Pseudolarix Acid B, a New Tubulin-Binding Agent, Inhibits Angiogenesis by Interacting with a Novel Binding Site on Tubulin

Yun-Guang Tong, Xiong-Wen Zhang, Mei-Yu Geng, Jian-Ming Yue, Xian-Liang Xin, Fang Tian, Xu Shen, Lin-Jiang Tong, Mei-Hong Li, Chao Zhang, Wei-Hong Li, Li-Ping Lin and Jian Ding
Molecular Pharmacology April 1, 2006, 69 (4) 1226-1233; DOI: https://doi.org/10.1124/mol.105.020537

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Research ArticleOriginal Article

Pseudolarix Acid B, a New Tubulin-Binding Agent, Inhibits Angiogenesis by Interacting with a Novel Binding Site on Tubulin

Yun-Guang Tong, Xiong-Wen Zhang, Mei-Yu Geng, Jian-Ming Yue, Xian-Liang Xin, Fang Tian, Xu Shen, Lin-Jiang Tong, Mei-Hong Li, Chao Zhang, Wei-Hong Li, Li-Ping Lin and Jian Ding
Molecular Pharmacology April 1, 2006, 69 (4) 1226-1233; DOI: https://doi.org/10.1124/mol.105.020537
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