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

doi:10.1038/s41598-017-12855-w

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)

University of East Anglia

Research output: Contribution to journal › Article › peer-review

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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 language	English
Article number	12651
Journal	Scientific Reports
Volume	7
DOIs	https://doi.org/10.1038/s41598-017-12855-w
Publication status	Published - 4 Oct 2017
Externally published	Yes

Bibliographical 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.

Keywords

cancer prevention
drug development
tumour angiogenesis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cite this

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

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.",

keywords = "cancer prevention, drug development, tumour angiogenesis",

author = "Peng Liu and Atkinson, {Samuel J} and Akbareian, {Sophia E.} and Zhigang Zhou and Andrea M{\"u}nsterberg and Stephen Robinson and Yongping Bao",

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 - Liu, Peng

AU - Atkinson, Samuel J

AU - Akbareian, Sophia E.

AU - Zhou, Zhigang

AU - Münsterberg, Andrea

AU - Robinson, Stephen

AU - Bao, Yongping

N1 - 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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Y1 - 2017/10/4

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.

AB - 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.

KW - cancer prevention

KW - drug development

KW - tumour angiogenesis

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M1 - 12651

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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