Literature DB >> 22703300

Novel dual inhibitors of vascular endothelial growth factor and VEGFR2 receptor.

Jennifer P Nguyen1, Chelsea D Frost, Meghan L Lane, William P Skelton, Michelle Skelton, David L Vesely.   

Abstract

BACKGROUND: Vascular endothelial growth factor (VEGF) helps control tumour growth via causing new capillaries growth in tumours. Four cardiac hormones [i.e. vessel dilator, long-acting natriuretic peptide (LANP), kaliuretic peptide (KP) and atrial natriuretic peptide (ANP)] that eliminate up to up to 86% of human small-cell lung cancers growing in mice were investigated for their effects on VEGF and the VEGFR2/KDR/Flk-1 receptor. The VEGFR2 receptor is the main receptor mediating VEGF's cancer-enhancing effects.
MATERIALS AND METHODS: Four cardiac hormones were evaluated for their ability to decrease VEGF/VEGFR2 measured by ELISAs in three human cancer cell lines.
RESULTS: Vessel dilator, LANP, KP and ANP, over a concentration range of 100 pM to 10 μM, maximally decreased the VEGFR2 receptor in human pancreatic adenocarcinoma cells by 48%, 49%, 74% and 83%. Vessel dilator, LANP, KP and ANP decreased the VEGFR2 receptor by 77%, 89%, 88% and 67% in human small-cell lung cancer cells and by 48%, 92%, 64% and 71% in human prostate cancer cells. These results were confirmed with the cardiac hormones also decreasing the VEGFR2 receptor measured by Western blots. VEGF itself in pancreatic carcinoma cells was decreased by 42%, 58%, 36% and 40% by vessel dilator, LANP, KP and ANP. VEGF levels were decreased 25%, 23%, 17% and 23% in small-cell lung cancer cells and decreased by 24%, 20%, 23% and 24% in prostate cancer cells by vessel dilator, LANP, KP and ANP.
CONCLUSION: Four cardiac hormones are the first dual inhibitors of VEGF and the VEGFR2/KDR/Flk-1 receptor.
© 2012 The Authors. European Journal of Clinical Investigation © 2012 Stichting European Society for Clinical Investigation Journal Foundation.

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Year:  2012        PMID: 22703300     DOI: 10.1111/j.1365-2362.2012.02695.x

Source DB:  PubMed          Journal:  Eur J Clin Invest        ISSN: 0014-2972            Impact factor:   4.686


  7 in total

1.  Endothelial cells enhance prostate cancer metastasis via IL-6→androgen receptor→TGF-β→MMP-9 signals.

Authors:  Xiaohai Wang; Soo Ok Lee; Shujie Xia; Qi Jiang; Jie Luo; Lei Li; Shuyuan Yeh; Chawnshang Chang
Journal:  Mol Cancer Ther       Date:  2013-03-27       Impact factor: 6.261

2.  Potent selective inhibition of STAT 3 versus STAT 1 by cardiac hormones.

Authors:  Meghan L Lane; Chelsea D Frost; Jennifer P Nguyen; William P Skelton; Michelle Skelton; David L Vesely
Journal:  Mol Cell Biochem       Date:  2012-09-11       Impact factor: 3.396

3.  N-Terminal Pro-Brain Natriuretic Peptide Is Associated with a Future Diagnosis of Cancer in Patients with Coronary Artery Disease.

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Journal:  PLoS One       Date:  2015-06-05       Impact factor: 3.240

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5.  Reduction of leptin levels by four cardiac hormones: Implications for hypertension in obesity.

Authors:  Meghan L Lane; David L Vesely
Journal:  Exp Ther Med       Date:  2013-06-21       Impact factor: 2.447

6.  Atrial natriuretic peptide: a magic bullet for cancer therapy targeting Wnt signaling and cellular pH regulators.

Authors:  A Serafino; P Pierimarchi
Journal:  Curr Med Chem       Date:  2014       Impact factor: 4.530

Review 7.  Modified natriuretic peptides and their potential roles in cancer treatment.

Authors:  Mengjiao Xu; Xingzhu Liu; Ping Li; Yadong Yang; Wenyuan Zhang; Siyu Zhao; Ying Zeng; Xile Zhou; Ling-Hui Zeng; Geng Yang
Journal:  Biomed J       Date:  2021-07-06       Impact factor: 7.892

  7 in total

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