Oleanolic Acids Inhibit Vascular Endothelial Growth Factor Receptor 2 Signaling in Endothelial Cells: Implication for Anti-Angiogenic Therapy

Overview

Journal Mol Cells

Publisher Elsevier

Specialties Cell Biology
Molecular Biology

Date 2018 Jul 25

PMID 30037214

Citations 8

Authors

Da-Hye Lee

Jungsul Lee

Jongwook Jeon

Kyung-Jin Kim

Jang-Hyuk Yun

Han-Seok Jeong

Eun Hui Lee

Young Jun Koh

Chung-Hyun Cho

Affiliations

Soon will be listed here.

Abstract

Angiogenesis must be precisely controlled because uncontrolled angiogenesis is involved in aggravation of disease symptoms. Vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR-2) signaling is a key pathway leading to angiogenic responses in vascular endothelial cells (ECs). Therefore, targeting VEGF/VEGFR-2 signaling may be effective at modulating angiogenesis to alleviate various disease symptoms. Oleanolic acid was verified as a VEGFR-2 binding chemical from anticancer herbs with similar binding affinity as a reference drug in the Protein Data Bank (PDB) entry 3CJG of model A coordination. Oleanolic acid effectively inhibited VEGF-induced VEGFR-2 activation and angiogenesis in HU-VECs without cytotoxicity. We also verified that oleanolic acid inhibits angiogenesis during the development and the course of the retinopathy of prematurity (ROP) model in the mouse retina. Taken together, our results suggest a potential therapeutic benefit of oleanolic acid for inhibiting angiogenesis in proangiogenic diseases, including retinopathy.

Citing Articles

Potential inhibitors of VEGFR1, VEGFR2, and VEGFR3 developed through Deep Learning for the treatment of Cervical Cancer.

Nayarisseri A, Abdalla M, Joshi I, Yadav M, Bhrdwaj A, Chopra I Sci Rep. 2024; 14(1):13251.

PMID: 38858458 PMC: 11164920. DOI: 10.1038/s41598-024-63762-w.

CD62E- and ROS-Responsive ETS Improves Cartilage Repair by Inhibiting Endothelial Cell Activation through OPA1-Mediated Mitochondrial Homeostasis.

Tu P, Pan Y, Wang L, Li B, Sun X, Liang Z Biomater Res. 2024; 28:0006.

PMID: 38439927 PMC: 10911934. DOI: 10.34133/bmr.0006.

Pro‑angiogenic activity of salvianolate and its potential therapeutic effect against acute cerebral ischemia.

Xu J, Shen Y, Luan P, Wang H, Xu Y, Jiang L Exp Ther Med. 2023; 26(2):409.

PMID: 37522065 PMC: 10375442. DOI: 10.3892/etm.2023.12108.

Antiproliferative Activity of (Willd.) against Melanoma and Modulation of Angiogenesis.

Twilley D, Thipe V, Kishore N, Bloebaum P, Roma-Rodrigues C, Baptista P Pharmaceuticals (Basel). 2022; 15(12).

PMID: 36558948 PMC: 9782150. DOI: 10.3390/ph15121497.

Sodium tanshinone IIA sulfonate ameliorates cerebral ischemic injury through regulation of angiogenesis.

Xu J, Zhang P, Chen Y, Xu Y, Luan P, Zhu Y Exp Ther Med. 2021; 22(4):1122.

PMID: 34504576 PMC: 8383733. DOI: 10.3892/etm.2021.10556.

References

Bikfalvi A . Recent developments in the inhibition of angiogenesis: examples from studies on platelet factor-4 and the VEGF/VEGFR system. Biochem Pharmacol. 2004; 68(6):1017-21. DOI: 10.1016/j.bcp.2004.05.030. View

Jeong D, Kim Y, Kim H, Ji H, Yoo S, Choi W . Dose-linear pharmacokinetics of oleanolic acid after intravenous and oral administration in rats. Biopharm Drug Dispos. 2006; 28(2):51-7. DOI: 10.1002/bdd.530. View

Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W . Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004; 350(23):2335-42. DOI: 10.1056/NEJMoa032691. View

Hanahan D, Folkman J . Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell. 1996; 86(3):353-64. DOI: 10.1016/s0092-8674(00)80108-7. View

Berman H, Westbrook J, Feng Z, Gilliland G, Bhat T, Weissig H . The Protein Data Bank. Nucleic Acids Res. 1999; 28(1):235-42. PMC: 102472. DOI: 10.1093/nar/28.1.235. View

Shoichet B . Virtual screening of chemical libraries. Nature. 2004; 432(7019):862-5. PMC: 1360234. DOI: 10.1038/nature03197. View

Liu J, Wu Q, Lu Y, Pi J . New insights into generalized hepatoprotective effects of oleanolic acid: key roles of metallothionein and Nrf2 induction. Biochem Pharmacol. 2008; 76(7):922-8. DOI: 10.1016/j.bcp.2008.07.021. View

Leung D, Cachianes G, Kuang W, Goeddel D, Ferrara N . Vascular endothelial growth factor is a secreted angiogenic mitogen. Science. 1989; 246(4935):1306-9. DOI: 10.1126/science.2479986. View

Ferrara N . Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev. 2004; 25(4):581-611. DOI: 10.1210/er.2003-0027. View

10.

Holash J, Davis S, Papadopoulos N, Croll S, Ho L, Russell M . VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci U S A. 2002; 99(17):11393-8. PMC: 123267. DOI: 10.1073/pnas.172398299. View

11.

Sapieha P, Joyal J, Rivera J, Kermorvant-Duchemin E, Sennlaub F, Hardy P . Retinopathy of prematurity: understanding ischemic retinal vasculopathies at an extreme of life. J Clin Invest. 2010; 120(9):3022-32. PMC: 2929716. DOI: 10.1172/JCI42142. View

12.

Laszczyk M . Pentacyclic triterpenes of the lupane, oleanane and ursane group as tools in cancer therapy. Planta Med. 2009; 75(15):1549-60. DOI: 10.1055/s-0029-1186102. View

13.

Aiello L . Angiogenic pathways in diabetic retinopathy. N Engl J Med. 2005; 353(8):839-41. DOI: 10.1056/NEJMe058142. View

14.

Gariano R, Gardner T . Retinal angiogenesis in development and disease. Nature. 2005; 438(7070):960-6. DOI: 10.1038/nature04482. View

15.

Petronelli A, Pannitteri G, Testa U . Triterpenoids as new promising anticancer drugs. Anticancer Drugs. 2009; 20(10):880-92. DOI: 10.1097/CAD.0b013e328330fd90. View

16.

Tang J, Kern T . Inflammation in diabetic retinopathy. Prog Retin Eye Res. 2011; 30(5):343-58. PMC: 3433044. DOI: 10.1016/j.preteyeres.2011.05.002. View

17.

Krady J, Basu A, Allen C, Xu Y, LaNoue K, Gardner T . Minocycline reduces proinflammatory cytokine expression, microglial activation, and caspase-3 activation in a rodent model of diabetic retinopathy. Diabetes. 2005; 54(5):1559-65. DOI: 10.2337/diabetes.54.5.1559. View

18.

Wells J, Murthy R, Chibber R, Nunn A, Molinatti P, Kohner E . Levels of vascular endothelial growth factor are elevated in the vitreous of patients with subretinal neovascularisation. Br J Ophthalmol. 1996; 80(4):363-6. PMC: 505466. DOI: 10.1136/bjo.80.4.363. View

19.

Yun J, Park S, Kim K, Bae J, Lee E, Paek S . Endothelial STAT3 Activation Increases Vascular Leakage Through Downregulating Tight Junction Proteins: Implications for Diabetic Retinopathy. J Cell Physiol. 2016; 232(5):1123-1134. DOI: 10.1002/jcp.25575. View

20.

Bernatchez P, Soker S, Sirois M . Vascular endothelial growth factor effect on endothelial cell proliferation, migration, and platelet-activating factor synthesis is Flk-1-dependent. J Biol Chem. 1999; 274(43):31047-54. DOI: 10.1074/jbc.274.43.31047. View