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Current Neurovascular Research

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ISSN (Print): 1567-2026
ISSN (Online): 1875-5739

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Research Article

Nanocurcumin Inhibits Angiogenesis via Down-regulating hif1a/VEGF-A Signaling in Zebrafish

Author(s): Zigang Cao, Shicong He, Yuyang Peng, Xinjun Liao* and Huiqiang Lu*

Volume 17, Issue 2, 2020

Page: [147 - 154] Pages: 8

DOI: 10.2174/1567202617666200207130039

Price: $65

Abstract

Background: Curcumin has anti-inflammatory, antioxidant and anticancer properties. Despite the considerable evidence showing that curcumin is an efficacious and safe compound for multiple medicinal benefits, there are some demerits with respect to the therapeutic effectiveness of curcumin, namely, poor stability and solubility, and its role in angiogenesis in vivo is still not yet clear. More recently, the biodegradable polymer nanoparticles have been developed. This offers promise for the therapeutic effectiveness of curcumin by increasing its bioavailability, solubility and retention time.

Methods: Here, we compared the medicinal effectiveness of curcumin and nanocurcumin (NC), and found that nanocurcumin can inhibit angiogenesis more effectively than curcumin in zebrafish. Tests of proliferation and apoptosis showed no difference between nanocurcumin-treated and wildtype embryos.

Results: qPCR and in situ hybridization experiments indicated that the VEGF signaling pathway genes, vegfa, VEGF-C and flt4 were all down-regulated after nanocurcumin treatment, and vegfa over-expression rescued the vascular defective phenotype. Moreover, hif1a expression also decreased and hif1a over-expression also rescued the vascular defective phenotype but the Notch signaling pathway had no difference after nanocurcumin treatment.

Conclusion: These results indicate that nano curcumin inhibits angiogenesis in zebrafish by downregulating hif1a/vegfa signaling pathway. Hence, our work reveals the key role of nanocurcumin in angiogenesis in vivo.

Keywords: Nanocurcumin, angiogenesis, Vegf, hif1a, zebrafish, anticancer, antioxidant.

« Previous Next »
[1]
Carmeliet P. Angiogenesis in health and disease. Nat Med 2003; 9(6): 653-60.
[http://dx.doi.org/10.1038/nm0603-653] [PMID: 12778163]
[2]
Parng C, Seng WL, Semino C, McGrath P. Zebrafish: A preclinical model for drug screening. Assay Drug Dev Technol 2002; 1(1 Pt 1): 41-8.
[http://dx.doi.org/10.1089/154065802761001293] [PMID: 15090155]
[3]
Roca C, Adams RH. Regulation of vascular morphogenesis by Notch signaling. Genes Dev 2007; 21(20): 2511-24.
[http://dx.doi.org/10.1101/gad.1589207] [PMID: 17938237]
[4]
Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis. Nature 2011; 473(7347): 298-307.
[http://dx.doi.org/10.1038/nature10144] [PMID: 21593862]
[5]
Bussmann J, Wolfe SA, Siekmann AF. Arterial-venous network formation during brain vascularization involves hemodynamic regulation of chemokine signaling. Development 2011; 138(9): 1717-26.
[http://dx.doi.org/10.1242/dev.059881] [PMID: 21429983]
[6]
Nasevicius A, Larson J, Ekker SC. Distinct requirements for zebrafish angiogenesis revealed by a VEGF-A morphant. Yeast 2000; 17(4): 294-301.
[http://dx.doi.org/10.1002/1097-0061(200012)17:4<294:AID-YEA54>3.0.CO;2-5] [PMID: 11119306]
[7]
Helker CS, Schuermann A, Karpanen T, et al. The zebrafish common cardinal veins develop by a novel mechanism: lumen ensheathment. Development 2013; 140(13): 2776-86.
[http://dx.doi.org/10.1242/dev.091876] [PMID: 23698350]
[8]
Herbert SP, Stainier DYR. Molecular control of endothelial cell behaviour during blood vessel morphogenesis. Nat Rev Mol Cell Biol 2011; 12(9): 551-64.
[http://dx.doi.org/10.1038/nrm3176] [PMID: 21860391]
[9]
Jiang BH, Semenza GL, Bauer C, Marti HH. Hypoxia-inducible factor 1 levels vary exponentially over a physiologically relevant range of O2 tension. Am J Physiol 1996; 271(4 Pt 1): C1172-80.
[http://dx.doi.org/10.1152/ajpcell.1996.271.4.C1172] [PMID: 8897823]
[10]
Semenza GL. Regulation of mammalian O2 homeostasis by hypoxia-inducible factor 1. Annu Rev Cell Dev Biol 1999; 15: 551-78.
[http://dx.doi.org/10.1146/annurev.cellbio.15.1.551] [PMID: 10611972]
[11]
Pagès G, Pouysségur J. Transcriptional regulation of the vascular endothelial growth factor gene--a concert of activating factors. Cardiovasc Res 2005; 65(3): 564-73.
[http://dx.doi.org/10.1016/j.cardiores.2004.09.032] [PMID: 15664382]
[12]
Aggarwal BB, Kumar A, Bharti AC. Anticancer potential of curcumin: Preclinical and clinical studies. Anticancer Res 2003; 23(1A): 363-98.
[PMID: 12680238]
[13]
Cai XZ, Wang J, Xiao Dong L, et al. Curcumin suppresses proliferation and invasion in human gastric cancer cells by downregulation of PAK1 activity and cyclin D1 expression. Cancer Biol Ther 2009; 8: 9-14.
[http://dx.doi.org/10.4161/cbt.8.14.8720]
[14]
Singh AK, Sidhu GS, Deepa T, Maheshwari RK. Curcumin inhibits the proliferation and cell cycle progression of human umbilical vein endothelial cell. Cancer Lett 1996; 107(1): 109-15.
[http://dx.doi.org/10.1016/0304-3835(96)04357-1] [PMID: 8913274]
[15]
Zhang Y, Cao H, Hu YY, Wang H, Zhang CJ. Inhibitory effect of curcumin on angiogenesis in ectopic endometrium of rats with experimental endometriosis. Int J Mol Med 2011; 27(1): 87-94.
[PMID: 21069258]
[16]
Flora G, Gupta D, Tiwari A. Nanocurcumin: a promising therapeutic advancement over native curcumin. Crit Rev Ther Drug Carrier Syst 2013; 30(4): 331-68.
[http://dx.doi.org/10.1615/CritRevTherDrugCarrierSyst.2013007236] [PMID: 23662605]
[17]
Arbiser JL, Klauber N, Rohan R, et al. Curcumin is an in vivo inhibitor of angiogenesis. Mol Med 1998; 4(6): 376-83.
[http://dx.doi.org/10.1007/BF03401744] [PMID: 10780880]
[18]
Mohan R, Sivak J, Ashton P, et al. Curcuminoids inhibit the angiogenic response stimulated by fibroblast growth factor-2, including expression of matrix metalloproteinase gelatinase B. J Biol Chem 2000; 275(14): 10405-12.
[http://dx.doi.org/10.1074/jbc.275.14.10405] [PMID: 10744729]
[19]
Thaloor D, Singh AK, Sidhu GS, Prasad PV, Kleinman HK, Maheshwari RK. Inhibition of angiogenic differentiation of human umbilical vein endothelial cells by curcumin. Cell Growth Differ 1998; 9(4): 305-12.
[PMID: 9563850]
[20]
Cao Z, Wang H, Mao X, Luo L. Noncanonical function of threonyl-tRNA synthetase regulates vascular development in zebrafish. Biochem Biophys Res Commun 2016; 473(1): 67-72.
[http://dx.doi.org/10.1016/j.bbrc.2016.03.051] [PMID: 26993167]
[21]
Jiang S, Zhu R, He X, et al. Enhanced photocytotoxicity of curcumin delivered by solid lipid nanoparticles. Int J Nanomedicine 2016; 12: 167-78.
[http://dx.doi.org/10.2147/IJN.S123107] [PMID: 28053531]
[22]
Chen J, He J, Li L, Yang D, Luo L. Cyp2aa9 regulates haematopoietic stem cell development in zebrafish. Sci Rep 2016; 6: 26608.
[http://dx.doi.org/10.1038/srep26608] [PMID: 27197559]
[23]
Lin TY, Chou CF, Chung HY, et al. Hypoxia-inducible factor 2 alpha is essential for hepatic outgrowth and functions via the regulation of leg1 transcription in the zebrafish embryo. PLoS One 2014; 9(7)e101980
[http://dx.doi.org/10.1371/journal.pone.0101980] [PMID: 25000307]
[24]
He J, Lu H, Zou Q, Luo L. Regeneration of liver after extreme hepatocyte loss occurs mainly via biliary transdifferentiation in zebrafish. Gastroenterology 2014; 146(3): 789-800.e8.
[http://dx.doi.org/10.1053/j.gastro.2013.11.045] [PMID: 24315993]
[25]
Cao Z, Mao X, Luo L. Germline stem cell drive ovary regeneration. Cell Rep 2019; 26(7): 1709-1717.e3.
[http://dx.doi.org/10.1016/j.celrep.2019.01.061] [PMID: 30759383]
[26]
Fu Z, Chen X, Guan S, Yan Y, Lin H, Hua ZC. Curcumin inhibits angiogenesis and improves defective hematopoiesis induced by tumor-derived VEGF in tumor model through modulating VEGFVEGFR2 signaling pathway. Oncotarget 2015; 6(23): 19469-82.
[http://dx.doi.org/10.18632/oncotarget.3625] [PMID: 26254223]
[27]
Bae MK, Kim SH, Jeong JW, et al. Curcumin inhibits hypoxiainduced angiogenesis via down-regulation of HIF-1. Vascul Pharmacol 2000; 45: e155-6.
[28]
Mahmood K, Zia KM, Zuber M, Salman M, Anjum MN. Recent developments in curcumin and curcumin based polymeric materials for biomedical applications: A review. Int J Biol Macromol 2015; 81: 877-90.
[http://dx.doi.org/10.1016/j.ijbiomac.2015.09.026] [PMID: 26391597]
[29]
Naksuriya O, Okonogi S, Schiffelers RM, Hennink WE. Curcumin nanoformulations:A review of pharmaceutical properties and preclinical studies and clinical data related to cancer treatment. Biomaterials 2014; 35(10): 3365-83.
[http://dx.doi.org/10.1016/j.biomaterials.2013.12.090] [PMID: 24439402]
[30]
Prasad S, Tyagi AK, Aggarwal BB. Recent developments in delivery, bioavailability, absorption and metabolism of curcumin: The golden pigment from golden spice. Cancer Res Treat 2014; 46(1): 2-18.
[http://dx.doi.org/10.4143/crt.2014.46.1.2] [PMID: 24520218]

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