Ponatinib exerts anti-angiogenic effects in the zebrafish and human umbilical vein endothelial cells via blocking VEGFR signaling pathway

Oncotarget
Nana AiWei Ge

Abstract

Angiogenesis is a hallmark for cancer development because it is essential for cancer growth and provides the route for cancer cell migration (metastasis). Understanding the mechanism of angiogenesis and developing drugs that target the process has therefore been a major focus for research on cancer therapy. In this study, we screened 114 FDA-approved anti-cancer drugs for their effects on angiogenesis in the zebrafish. Among those with positive effects, we chose to focus on Ponatinib (AP24534; Iclusig®) for further investigation. Ponatinib is an inhibitor of the tyrosine kinase BCR-ABL in chronic myeloid leukemia (CML), and its clinical trial has been approved by FDA for the treatment of the disease. In recent clinical trials, however, some side effects have been reported for Ponatinib, mostly on blood vessel disorders, raising the possibility that this drug may influence angiogenesis. In this study, we demonstrated that Ponatinib was able to suppress the formation of intersegmental vessels (ISV) and subintestinal vessels (SIV) in the zebrafish larvae. The anti-angiogenic effect of Ponatinib was further validated by other bioassays in human umbilical vein endothelial cells (HUVECs), including cell proliferation and migration, t...Continue Reading

References

Oct 14, 1988·Biochemical and Biophysical Research Communications·Y TotsukaE Ogata
Nov 18, 1971·The New England Journal of Medicine·J Folkman
May 29, 1998·Developmental Dynamics : an Official Publication of the American Association of Anatomists·M S LyonsK G Peters
Jan 27, 2000·Cell·D Hanahan, R A Weinberg
Sep 23, 2000·Nature·P Carmeliet, R K Jain
Jan 10, 2002·Nature Cell Biology·Marika J KarkkainenKari Alitalo
Jun 29, 2002·Circulation Research·Ichiro Shiojima, Kenneth Walsh
Jan 1, 2003·Clinical Chemistry·Robert AuerbachNasim Akhtar
Jan 17, 2003·Cell Research·Weiming XuIan G Charles
Sep 6, 2003·The Journal of Pharmacy and Pharmacology·Tayade PralhadKale Rajendrakumar
Oct 1, 2003·Angiogenesis·G N SerbedzijaC E Willett
Dec 25, 2003·The Journal of Pathology·H M W VerheulR O Schlingemann
May 28, 2004·Trends in Molecular Medicine·Dan G DudaRakesh K Jain
Sep 6, 2005·Proceedings of the National Academy of Sciences of the United States of America·Lisa A RidnourDavid A Wink
Nov 23, 2005·Oncology·Peter Carmeliet
Feb 2, 2006·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Misato FujitaAkira Kudo
Apr 25, 2006·Nature Reviews. Molecular Cell Biology·Anna-Karin OlssonLena Claesson-Welsh
Mar 31, 2007·Circulation Research·Laurent LamaliceJacques Huot
Apr 23, 2008·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Jing-Wei Xiong
May 13, 2008·Drug Discovery Today·Patricia McGrath, Chun-Qi Li
Jan 28, 2009·Nature Chemical Biology·Jing-Ruey J YehRandall T Peterson
Aug 15, 2009·Cell Communication and Signaling : CCS·Thomas SeufferleinGötz von Wichert
Sep 9, 2009·Nature Reviews. Clinical Oncology·S Percy IvyBennett M Kaufman
Jun 22, 2012·Human Reproduction Update·M W Laschke, M D Menger
Oct 3, 2012·Cold Spring Harbor Perspectives in Medicine·Kellen L Meadows, Herbert I Hurwitz
Nov 30, 2012·The New England Journal of Medicine·Jorge E CortesMoshe Talpaz
Feb 5, 2014·Redox Biology·Miriam M Cortese-Krott, Malte Kelm
Feb 7, 2014·Natural Product Research·Min XuYing-Jun Zhang
Feb 19, 2014·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·J ZhouC-Q Li
Jul 6, 2014·Chemical Biology & Drug Design·Chunlei TangBainian Feng
Sep 3, 2014·Redox Biology·Miriam M Cortese-KrottChristoph V Suschek
Oct 28, 2014·Journal of Applied Toxicology : JAT·Rui YangChun-Qi Li

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Citations

May 1, 2021·Journal of Thrombosis and Haemostasis : JTH·Nathan Watson, Hanny Al-Samkari
May 30, 2021·Translational Stroke Research·Weijie ChenPeiying Li
May 18, 2021·Evidence-based Complementary and Alternative Medicine : ECAM·Wenjing DongWu Dong

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Methods Mentioned

BETA
transgenic
protein assay

Software Mentioned

Prism
Bio
GraphPad
EVOS Cell
NIH image J
Rad Image Lab

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