Effects of Allium sativum Stem Extract on Growth and Migration in Melanoma Cells through Inhibition of VEGF, MMP-2, and MMP-9 Genes Expression

Molecules. 2021 Dec 21;27(1):21. doi: 10.3390/molecules27010021.

Abstract

The present study investigated the effects of Allium sativum stem extract (ASE) on B16-F0 cell growth and metastasis. Evaluation of the effects of ASE on B16-F0 cells' viability and migration showed that 0.5 mg/mL ASE inhibited B16-F0 cells' growth by 30.2% and migration by 38.5%, which indicates that the ASE has anticancer and antimetastatic effects on B16-F0 cells. To study the anticancer and antimetastatic mechanism, mRNA levels of vascular endothelial growth factor (VEGF), matrix metalloproteinases-2 (MMP-2), and matrix metalloproteinases-9 (MMP-9) expressions were evaluated with reverse transcription polymerase chain reaction, and 0.25 and 0.5 mg/mL ASE was found to exert significant inhibition on mRNA expressions of VEGF, MMP-2, and MMP-9 in B16-F0 cells. Thus, ASE reduce extracellular matrix degradation through inhibitions of expression of MMP-2 and MMP-9, and also showed an angiogenesis inhibitory effect through reduction of VEGF expression. High-performance liquid chromatography analysis showed that among various polyphenols, gallic acid (2.1 mg/g) was a major compound of ASE. Overall, our results demonstrated that ASE inhibited the growth and migration of B16-F0 cells through downregulation of the VEGF, MMP-2, and MMP-9 genes expression, which indicates ASE could be applied for the prevention and treatment of melanoma.

Keywords: Allium sativum stem; MMP-2; MMP-9; VEGF; anticancer; antimetastasis; gallic acid.

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Drug Screening Assays, Antitumor
  • Gallic Acid / chemistry*
  • Gallic Acid / pharmacology
  • Garlic / chemistry*
  • Humans
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Melanoma / drug therapy*
  • Plant Extracts / chemistry*
  • Plant Extracts / pharmacology
  • Plant Stems / chemistry*
  • RNA, Messenger / drug effects
  • Vascular Endothelial Growth Factors / genetics
  • Vascular Endothelial Growth Factors / metabolism
  • Wound Healing / drug effects

Substances

  • Antineoplastic Agents
  • Plant Extracts
  • RNA, Messenger
  • Vascular Endothelial Growth Factors
  • Gallic Acid
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9