A novel angiogenesis inhibitor impairs lovo cell survival via targeting against human VEGFR and its signaling pathway of phosphorylation

Y. M. Zhang, B. L. Dai, L. Zheng, Y. Z. Zhan, J. Zhang, Wanli Smith, X. L. Wang, Y. N. Chen, L. C. He

Research output: Contribution to journalArticle

Abstract

Colorectal cancer represents the fourth commonest malignancy, and constitutes a major cause of significant morbidity and mortality among other diseases. However, the chemical therapy is still under development. Angiogenesis plays an important role in colon cancer development.We developed HMQ18-22 (a novel analog of taspine) with the aim to target angiogenesis. We found that HMQ18-22 significantly reduced angiogenesis of chicken chorioallantoic membrane (CAM) and mouse colon tissue, and inhibited cell migration and tube formation as well. Then, we verified the interaction between HMQ18-22 and VEGFR2 by AlphaScreen P-VEGFR assay, screened the targets on angiogenesis by VEGF Phospho Antibody Array, validated the target by western blot and RNAi in lovo cells. We found HMQ18-22 could decrease phosphorylation of VEGFR2(Tyr1214), VEGFR1(Tyr1333), Akt(Tyr326), protein kinase Cα (PKCα) (Tyr657) and phospholipase-Cγ-1 (PLCγ-1) (Tyr771). Most importantly, HMQ18-22 inhibited proliferation of lovo cell and tumor growth in a human colon tumor xenografted model of athymic mice. Compared with normal lovo cells proliferation, the inhibition on proliferation of knockdown cells (VEGFR2, VEGFR1, Akt, PKCα and PLCγ-1) by HMQ18-22 decreased. These results suggested that HMQ18-22 is a novel angiogenesis inhibitor and can be a useful therapeutic candidate for colon cancer intervention.

Original languageEnglish (US)
Article numbere406
JournalCell Death and Disease
Volume3
Issue number10
DOIs
StatePublished - Oct 2012
Externally publishedYes

Fingerprint

Angiogenesis Inhibitors
Cell Survival
Phosphorylation
Cell Proliferation
Type C Phospholipases
Colonic Neoplasms
Protein Kinase C
Colon
Chorioallantoic Membrane
Neoplasms
RNA Interference
HMQ18-22
Nude Mice
Vascular Endothelial Growth Factor A
Cell Movement
Colorectal Neoplasms
Chickens
Western Blotting
Morbidity
Mortality

Keywords

  • Angiogenesis
  • HMQ18-22
  • Inhibition
  • Signaling pathway
  • VEGFR

ASJC Scopus subject areas

  • Cell Biology
  • Immunology
  • Cancer Research
  • Cellular and Molecular Neuroscience

Cite this

A novel angiogenesis inhibitor impairs lovo cell survival via targeting against human VEGFR and its signaling pathway of phosphorylation. / Zhang, Y. M.; Dai, B. L.; Zheng, L.; Zhan, Y. Z.; Zhang, J.; Smith, Wanli; Wang, X. L.; Chen, Y. N.; He, L. C.

In: Cell Death and Disease, Vol. 3, No. 10, e406, 10.2012.

Research output: Contribution to journalArticle

Zhang, Y. M. ; Dai, B. L. ; Zheng, L. ; Zhan, Y. Z. ; Zhang, J. ; Smith, Wanli ; Wang, X. L. ; Chen, Y. N. ; He, L. C. / A novel angiogenesis inhibitor impairs lovo cell survival via targeting against human VEGFR and its signaling pathway of phosphorylation. In: Cell Death and Disease. 2012 ; Vol. 3, No. 10.
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AU - Dai, B. L.

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AU - Zhan, Y. Z.

AU - Zhang, J.

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AB - Colorectal cancer represents the fourth commonest malignancy, and constitutes a major cause of significant morbidity and mortality among other diseases. However, the chemical therapy is still under development. Angiogenesis plays an important role in colon cancer development.We developed HMQ18-22 (a novel analog of taspine) with the aim to target angiogenesis. We found that HMQ18-22 significantly reduced angiogenesis of chicken chorioallantoic membrane (CAM) and mouse colon tissue, and inhibited cell migration and tube formation as well. Then, we verified the interaction between HMQ18-22 and VEGFR2 by AlphaScreen P-VEGFR assay, screened the targets on angiogenesis by VEGF Phospho Antibody Array, validated the target by western blot and RNAi in lovo cells. We found HMQ18-22 could decrease phosphorylation of VEGFR2(Tyr1214), VEGFR1(Tyr1333), Akt(Tyr326), protein kinase Cα (PKCα) (Tyr657) and phospholipase-Cγ-1 (PLCγ-1) (Tyr771). Most importantly, HMQ18-22 inhibited proliferation of lovo cell and tumor growth in a human colon tumor xenografted model of athymic mice. Compared with normal lovo cells proliferation, the inhibition on proliferation of knockdown cells (VEGFR2, VEGFR1, Akt, PKCα and PLCγ-1) by HMQ18-22 decreased. These results suggested that HMQ18-22 is a novel angiogenesis inhibitor and can be a useful therapeutic candidate for colon cancer intervention.

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