Kaempferol inhibits the cell migration of human hepatocellular carcinoma cells by suppressing MMP-9 and Akt signaling

Environ Toxicol. 2021 Oct;36(10):1981-1989. doi: 10.1002/tox.23316. Epub 2021 Jun 22.

Abstract

Metastasis is the most prevalent cause of cancer-related deaths and treatment failure in patients with hepatocellular carcinoma (HCC). Kaempferol is a natural flavonol belonging to the subgroup of flavonoids and exhibits potent anticancer activities. This study provides molecular evidence on the anti-invasive and anti-migratory effects of kaempferol on human HCC cells. The anti-invasive effect was investigated by applying kaempferol on two human HCC cell lines (Huh-7 and SK-Hep-1). Kaempferol reduced the invasion and migration of Huh-7 and SK-Hep-1 cells by Boyden chamber invasion assay and wound healing assay, respectively. A protease array analysis showed that Matrix Metalloproteinase-9 (MMP-9) was dramatically downregulated in HCC cells after kaempferol treatment. Gelatin zymography and Western blot assay showed that kaempferol reduced the activities and protein expression of MMP-9, respectively. Kaempferol also sufficiently suppressed the phosphorylation of the Akt expression. Overall, kaempferol inhibited the invasive properties of human HCC cells by targeting MMP-9 and Akt pathways. Hence, kaempferol could be used as an adjuvant therapeutic agent for the treatment of human HCC cells.

Keywords: HCC; MMP-9; kaempferol; migration.

MeSH terms

  • Carcinoma, Hepatocellular* / drug therapy
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement
  • Humans
  • Kaempferols / pharmacology
  • Liver Neoplasms* / drug therapy
  • Matrix Metalloproteinase 9* / genetics
  • Matrix Metalloproteinase 9* / metabolism
  • Neoplasm Invasiveness
  • Proto-Oncogene Proteins c-akt / genetics

Substances

  • Kaempferols
  • Proto-Oncogene Proteins c-akt
  • MMP9 protein, human
  • Matrix Metalloproteinase 9