Carvacrol Targets AXL to Inhibit Cell Proliferation and Migration in Non-small Cell Lung Cancer Cells

Anticancer Res. 2018 Jan;38(1):279-286. doi: 10.21873/anticanres.12219.

Abstract

Background/aim: AXL has been reported to be overexpressed and highly activated in various cancer types. In this study, we demonstrated the effect of carvacrol on cell proliferation and migration in non-small cell lung cancer (NSCLC) cells by impeding the expression and activation of AXL.

Materials and methods: The levels of AXL protein, mRNA and promoter activity were evaluated by western blot, reverse transcription polymerase chain reaction (RT-PCR) and luciferase assay, respectively. AXL-overexpressing cells were established by ectopic expression of AXL cDNA. Cell viability, clonogenicity, and migration were measured in carvacrol-treated NSCLC cells.

Results: Carvacrol treatment of NSCLC cells caused down-regulation of AXL expression at the transcriptional level and also inhibited phosphorylation of AXL upon ligand stimulation. Carvacrol suppressed cell proliferation and migration and its inhibitory effect was attenuated in AXL-overexpressing NSCLC cells.

Conclusion: Our data demonstrate that AXL is a crucial therapeutic target of carvacrol-induced inhibition of NSCLC cell proliferation and migration.

Keywords: AXL; NSCLC; carvacrol; migration; proliferation.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cymenes
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Monoterpenes / pharmacology*
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins / antagonists & inhibitors*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism

Substances

  • Antineoplastic Agents
  • Cymenes
  • Monoterpenes
  • Proto-Oncogene Proteins
  • carvacrol
  • Receptor Protein-Tyrosine Kinases
  • axl receptor tyrosine kinase