Zerumbone Suppresses Angiogenesis in HepG2 Cells through Inhibition of Matrix Metalloproteinase-9, Vascular Endothelial Growth Factor, and Vascular Endothelial Growth Factor Receptor Expressions.

CONTEXT

Due to increase in the number of patients with impaired immunity, the incidence of liver cancer has increased considerably.

AIMS

The aim of this study is the investigation the anticancer effect of zerumbone (ZER) on hepatocellular carcinoma (HCC).

MATERIALS AND METHODS

The anticancer mechanism of ZER was determined by the rat aortic ring, human umbilical vein endothelial cells (HUVECs) proliferation, chorioallantoic membrane, cell migration, and proliferation inhibition assays.

RESULTS

Our results showed that ZER reduced tube formation by HUVECs effectively inhibits new blood vessel and tissue matrix formation. Western blot analysis revealed that ZER significantly ( < 0.05) decreased expression of molecular effectors of angiogenesis, the matrix metalloproteinase-9, vascular endothelial growth factor (VEGF), and VEGF receptor proteins. We found that ZER inhibited the proliferation and suppressed migration of HepG2 cell in dose-dependent manner.

STATISTICAL ANALYSIS USED

Statistical analyses were performed according to the Statistical Package for Social Science (SPSS) version 17.0. The data were expressed as the mean ± standard deviation and analyzed using a one-way analysis of variance. A < 0.05 was considered statistically significant.

CONCLUSION

The study for the first time showed that ZER is an inhibitor angiogenesis, tumor growth, and spread, which is suggested to be the mechanisms for its anti-HCC effect.

SUMMARY

Tumor angiogenesis has currently become an important research area for the control of cancer growth and metastasis. The current study determined the effect of zerumbone on factors associated with angiogenesis that occurs in tumor formation. ZER: Zerumbone, MMP-9: Matrix metalloproteinase-9, VEGF: Vascular endothelial growth factor, VEGFR: Vascular endothelial growth factor receptor, HUVECs: Human umbilical vein endothelial cells, HCC: Hepatocellular carcinoma, HIFCS: Heat inactivated fetal calf serum, DMSO: Dimethyl sulfoxide, EDTA: Ethyldiaminetetraacetic acid, Ig: Immunoglobulin, CAM: Chorioallantoic membrane, HRP: Horseradish peroxidase, NIH: National Institutes of Health, MTT: Microtetrazolium, SPSS: Statistical Package for Social Science.