Kaempferol Inhibits the Invasion and Migration of Renal Cancer Cells through the Downregulation of AKT and FAK Pathways

Int J Med Sci. 2017 Aug 18;14(10):984-993. doi: 10.7150/ijms.20336. eCollection 2017.

Abstract

Kaempferol, which is isolated from several natural plants, is a polyphenol belonging to the subgroup of flavonoids. Kaempferol exhibits various pharmacological activities, including anti-inflammatory, antioxidant, antimicrobial, and anticancer activities. In this study, kaempferol can significantly inhibit the invasion and migration of 786-O renal cell carcinoma (RCC) without cytotoxicity. We examined the potential mechanisms underlying its anti-invasive activities on 786-O RCC cells. Western blot was performed, and the results showed that kaempferol attenuates the manifestation of metalloproteinase-2 (MMP-2) protein and activity. The inhibitive effect of kaempferol on MMP-2 may be attributed to the downregulation of phosphorylation of Akt and focal adhesion kinase (FAK). By examining the SCID mice model, we found that kaempferol can safely inhibit the metastasis of the 786-O RCC cells into the lungs by about 87.4% as compared to vehicle treated control animals. In addition, the lung tumor masses of mice pretreated with 2-10 mg/kg kaempferol were reduced about twofold to fourfold. These data suggested that kaempferol can play a promising role in tumor prevention and cancer metastasis inhibition.

Keywords: invasion.; kaempferol; metastasis; renal cell carcinoma.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / secondary
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Down-Regulation
  • Female
  • Focal Adhesion Kinase 1 / metabolism
  • Humans
  • Kaempferols / pharmacology*
  • Kaempferols / therapeutic use
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / secondary
  • Matrix Metalloproteinase 2 / metabolism
  • Mice
  • Mice, SCID
  • Neoplasm Invasiveness
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects*
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Kaempferols
  • kaempferol
  • Focal Adhesion Kinase 1
  • PTK2 protein, human
  • Proto-Oncogene Proteins c-akt
  • MMP2 protein, human
  • Matrix Metalloproteinase 2