Sulforaphane exerts anti-angiogenesis effects against hepatocellular carcinoma through inhibition of STAT3/HIF-1α/VEGF signalling

Peng Liu, Samuel J Atkinson, Sophia E. Akbareian, Zhigang Zhou, Andrea Münsterberg, Stephen Robinson, Yongping Bao (Corresponding Author)

Research output: Contribution to journalArticle

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Abstract

Angiogenesis plays an important role in hepatocellular carcinoma (HCC), the inhibition of which is explored for cancer prevention and treatment. The dietary phytochemical sulforaphane (SFN) is known for its anti-cancer properties in vitro and in vivo; but until now, no study has focused on the role of SFN in HCC tumor angiogenesis. In the present study, in vitro cell models using a HCC cell line, HepG2, and human endothelial cells, HUVECs, as well as ex vivo and in vivo models have been used to investigate the anti-tumor and anti-angiogenic effect of SFN. The results showed that SFN decreased HUVEC cell viability, migration and tube formation, all of which are important steps in angiogenesis. More importantly, SFN markedly supressed HepG2-stimulated HUVEC migration, adhesion and tube formation; which may be due to its inhibition on STAT3/HIF-1α/VEGF signalling in HepG2 cells. In addition, SFN significantly reduced HepG2 tumor growth in a modified chick embryo chorioallantoic membrane (CAM) assay, associated with a decrease of HIF-1α and VEGF expression within tumors. Collectively, these findings provide new insights into the inhibitory effect of SFN on HCC tumor angiogenesis as well as tumor growth, and indicate that SFN has potential for the prevention and treatment of HCC.

Original languageEnglish
Article number12651
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 4 Oct 2017

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Angiogenesis Inhibitors
Vascular Endothelial Growth Factor A
Hepatocellular Carcinoma
Neoplasms
Chorioallantoic Membrane
sulforafan
Human Umbilical Vein Endothelial Cells
Hep G2 Cells
Phytochemicals
Chick Embryo
Growth
Cell Movement
Cell Survival
Endothelial Cells
Cell Line

Keywords

  • cancer prevention
  • drug development
  • tumour angiogenesis

Cite this

Sulforaphane exerts anti-angiogenesis effects against hepatocellular carcinoma through inhibition of STAT3/HIF-1α/VEGF signalling. / Liu, Peng; Atkinson, Samuel J; Akbareian, Sophia E. ; Zhou, Zhigang; Münsterberg, Andrea; Robinson, Stephen; Bao, Yongping (Corresponding Author).

In: Scientific Reports, Vol. 7, 12651, 04.10.2017.

Research output: Contribution to journalArticle

Liu, Peng ; Atkinson, Samuel J ; Akbareian, Sophia E. ; Zhou, Zhigang ; Münsterberg, Andrea ; Robinson, Stephen ; Bao, Yongping. / Sulforaphane exerts anti-angiogenesis effects against hepatocellular carcinoma through inhibition of STAT3/HIF-1α/VEGF signalling. In: Scientific Reports. 2017 ; Vol. 7.
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abstract = "Angiogenesis plays an important role in hepatocellular carcinoma (HCC), the inhibition of which is explored for cancer prevention and treatment. The dietary phytochemical sulforaphane (SFN) is known for its anti-cancer properties in vitro and in vivo; but until now, no study has focused on the role of SFN in HCC tumor angiogenesis. In the present study, in vitro cell models using a HCC cell line, HepG2, and human endothelial cells, HUVECs, as well as ex vivo and in vivo models have been used to investigate the anti-tumor and anti-angiogenic effect of SFN. The results showed that SFN decreased HUVEC cell viability, migration and tube formation, all of which are important steps in angiogenesis. More importantly, SFN markedly supressed HepG2-stimulated HUVEC migration, adhesion and tube formation; which may be due to its inhibition on STAT3/HIF-1α/VEGF signalling in HepG2 cells. In addition, SFN significantly reduced HepG2 tumor growth in a modified chick embryo chorioallantoic membrane (CAM) assay, associated with a decrease of HIF-1α and VEGF expression within tumors. Collectively, these findings provide new insights into the inhibitory effect of SFN on HCC tumor angiogenesis as well as tumor growth, and indicate that SFN has potential for the prevention and treatment of HCC.",
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note = "This research was supported by a UEA International PhD Studentship to P. Liu, a BBSRC DTP PhD studentship to S. Atkinson, a grant from British Heart Foundation (PG/15/25/31369) to S. Robinson and an award from the Cancer Prevention Research Trust (UK) to Y. Bao.",
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AU - Atkinson, Samuel J

AU - Akbareian, Sophia E.

AU - Zhou, Zhigang

AU - Münsterberg, Andrea

AU - Robinson, Stephen

AU - Bao, Yongping

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N2 - Angiogenesis plays an important role in hepatocellular carcinoma (HCC), the inhibition of which is explored for cancer prevention and treatment. The dietary phytochemical sulforaphane (SFN) is known for its anti-cancer properties in vitro and in vivo; but until now, no study has focused on the role of SFN in HCC tumor angiogenesis. In the present study, in vitro cell models using a HCC cell line, HepG2, and human endothelial cells, HUVECs, as well as ex vivo and in vivo models have been used to investigate the anti-tumor and anti-angiogenic effect of SFN. The results showed that SFN decreased HUVEC cell viability, migration and tube formation, all of which are important steps in angiogenesis. More importantly, SFN markedly supressed HepG2-stimulated HUVEC migration, adhesion and tube formation; which may be due to its inhibition on STAT3/HIF-1α/VEGF signalling in HepG2 cells. In addition, SFN significantly reduced HepG2 tumor growth in a modified chick embryo chorioallantoic membrane (CAM) assay, associated with a decrease of HIF-1α and VEGF expression within tumors. Collectively, these findings provide new insights into the inhibitory effect of SFN on HCC tumor angiogenesis as well as tumor growth, and indicate that SFN has potential for the prevention and treatment of HCC.

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