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Wang, Yichong, Zhou, Zhigang, Wang, Wei, Liu, Ming and Bao, Yongping 
ORCID: https://orcid.org/0000-0002-6425-0370
(2017)
Differential effects of sulforaphane in regulation of angiogenesis in a co-culture model of endothelial cells and pericytes.
Oncology Reports, 37 (5).
pp. 2905-2912.
ISSN 1021-335X
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Abstract
Aberrant neovascularization supports nutrients and the oxygen microenvironment in tumour growth, invasion and metastasis. Recapitulation of functional microvascular structures in vitro could provide a platform for the study of vascular conditions. Sulforaphane (SFN), an isothiocyanate, has been reported to possess chemopreventive properties. In the present study, the effects of SFN on cell proliferation and tubular formation have been investigated using endothelial cells (ECs) and pericytes in coculture. SFN showed a dose-dependent inhibition on the growth of ECs and pericytes with IC50 values 46.7 and 32.4 µM, respectively. SFN (5-20 µM) inhibited tube formation in a 3D coculture although a lower dose (1.25 µM) promoted 30% more endothelial tube formation than control. Moreover, SFN affected intercellular communication between ECs and pericytes via inhibition of angiogenic factor such as vascular endothelial growth factor (VEGF) expression in pericytes. However, the expression of its receptor (VEGFR-2) was found significantly increased in ECs. These effects were associated with down-regulation of prolyl hydroxylase domain-containing protein 1 and 2 (PHD1/2) and activation of hypoxia-inducible factor-1 (HIF) pathway by SFN. Furthermore, thioredoxin reductase-1 was also up-regulated by SFN treatment, suggesting that anti-oxidant and redox regulation are involved in angiogenesis. Taken together, the results of this study suggest that SFN differentially regulates endothelial cells and pericytes, and disrupting their interplay through the VEGF-VEGFR signalling pathway. Anti-angiogenesis property of SFN indicates it has potential role as anticancer agent.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | sulforaphane, angiogenesis,pericyte,vegf,huvecs |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Groups > Nutrition and Preventive Medicine Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health |
| Related URLs: | |
| Depositing User: | Pure Connector |
| Date Deposited: | 11 Apr 2017 05:09 |
| Last Modified: | 13 Nov 2023 17:34 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/63214 |
| DOI: | 10.3892/or.2017.5565 |
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