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

• Published in: Scientific reports 2017-10, Vol.7 (1), p.12651-11, Article 12651
• Main Authors: Liu, Peng, Atkinson, Samuel J., Akbareian, Sophia E., Zhou, Zhigang, Munsterberg, Andrea, Robinson, Stephen D., Bao, Yongping
• Format: Article
• Language: English
• Subjects: 631/67/1059/153; 631/67/2195; 631/67/2328; Angiogenesis; Animals; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - pathology; Cell culture; Cell Movement - drug effects; Cell Proliferation - drug effects; Cell Survival - drug effects; Chick Embryo; Chorioallantoic membrane; Endothelial cells; Gene Expression Regulation, Neoplastic - drug effects; Hep G2 Cells; Hepatocellular carcinoma; Human Umbilical Vein Endothelial Cells; Humanities and Social Sciences; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Isothiocyanates - pharmacology; Liver cancer; Liver Neoplasms - drug therapy; Liver Neoplasms - genetics; Liver Neoplasms - pathology; multidisciplinary; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - genetics; Neovascularization, Pathologic - pathology; Prevention; Science; Science (multidisciplinary); Signal Transduction - drug effects; Stat3 protein; STAT3 Transcription Factor - genetics; Sulforaphane; Tumors; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - genetics
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-12855-w

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.