In vivo attenuation of angiogenesis in hepatocellular carcinoma by Nigella sativa

Turk J Med Sci. 2018 Feb 23;48(1):178-186. doi: 10.3906/sag-1701-86.

Abstract

Background/aim: Angiogenesis is imperative in malignant tumor growth. Hepatocellular carcinoma is a typical hypervascular tumor that relies on angiogenesis. The aim of this study is to investigate the in vivo molecular mechanism underlying the antitumor properties of Nigella sativa ethanolic extract (NSEE) through its antiangiogenic effect against diethyl nitrosamine (DENA)-induced hepatocarcinogenesis. Materials and methods: Male Wistar rats were divided into 4 groups: normal, NSEE, DENA, and NSEE-DENA groups. Final body weight, hepatosomatic indices, serum AFP, serum vascular endothelial growth factor (VEGF) levels, and liver tissue hepatocyte growth factor ß (HGFß) protein expression were estimated. Liver sections were stained for histological examination. AFP levels with the histological variations were chosen to confirm cancer development. Results: DENA significantly increased liver weight, hepatosomatic indices, serum AFP and VEGF levels, and liver HGFß protein expression and significantly decreased final body weight. These effects were significantly reversed by NSEE. Furthermore, the histopathological changes that appeared in rat livers due to DENA were reduced by NSEE without harmful effects when taken alone. Conclusion: The results of the present investigation provide evidence that the in vivo antiangiogenic effect of NSEE through downregulation of serum VEGF and liver HGFß protein could be implicated in its antitumor activity. Its consumption has health benefits that favor liver cancer management. These findings might prove useful and helpful for the progression of therapies for hepatocarcinogenesis treatment.

Keywords: Nigella sativa ethanolic extract; angiogenesis; hepatocarcinogenesis; vascular endothelial growth factor; hepatocyte growth factor β.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Carcinoma, Hepatocellular / blood*
  • Carcinoma, Hepatocellular / chemically induced
  • Carcinoma, Hepatocellular / drug therapy
  • Diethylnitrosamine
  • Liver / drug effects*
  • Liver / pathology
  • Liver Neoplasms / blood*
  • Liver Neoplasms / chemically induced
  • Liver Neoplasms / drug therapy
  • Male
  • Neovascularization, Pathologic / blood*
  • Neovascularization, Pathologic / drug therapy
  • Nigella sativa*
  • Phytotherapy
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use
  • Rats, Wistar
  • Vascular Endothelial Growth Factor A / blood

Substances

  • Antineoplastic Agents, Phytogenic
  • Plant Extracts
  • Vascular Endothelial Growth Factor A
  • Diethylnitrosamine