Zerumbone suppresses angiogenesis in HepG2 cells through inhibition of matrix Metalloproteinase-9, vascular endothelial growth factor, and vascular endothelial growth factor receptor expressions
Nozlena Abdul Samad1, Ahmad Bustamam Abdul2, Heshu Sulaiman Rahman3, Abdullah Rasedee4, Tengku Azmi Tengku Ibrahim4, Yeap Swee Keon4
1 UPM-MAKNA, Cancer Research Laboratory, Institute of Bioscience, Universiti Putra, Malaysia, 43400 UPM Serdang, Selangor; Integrative Medicine Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, 13200 Kepala Batas, Penang, Malaysia
2 UPM-MAKNA, Cancer Research Laboratory, Institute of Bioscience, Universiti Putra, Malaysia, 43400 UPM Serdang, Selangor, Malaysia
3 Department of Clinic and Internal Medicine, College of Veterinary Medicine, University of Sulaimani; Department of Medical Laboratory Sciences, College of Health Sciences, Komar University of Science and Technology, Chaq Chaq Qularaese, Sulaimani City, Kurdistan Region, Northern Iraq; Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
4 UPM-MAKNA, Cancer Research Laboratory, Institute of Bioscience, Universiti Putra, Malaysia, 43400 UPM Serdang; Department of Veterinary Laboratory Diagnosis, Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
Nozlena Abdul Samad
Integrative Medicine Cluster, Advance Medical and Dental Institute, University Sains Malaysia, 13200 Bertam Kepala Batas, Penang
Source of Support: None, Conflict of Interest: None
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 in vitro 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 (P < 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 P < 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.
Abbreviations used: 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.