Ethyl acetate extract from Inula helenium L. inhibits the proliferation of pancreatic cancer cells by regulating the STAT3/AKT pathway

Mol Med Rep. 2018 Apr;17(4):5440-5448. doi: 10.3892/mmr.2018.8534. Epub 2018 Feb 1.

Abstract

Sesquiterpene lactones are bioactive compounds that have been identified as responsible for the anticancer activity of the medicinal herb, Inula helenium L. (IHL). However, the mechanisms of action involved in the anti‑pancreatic cancer activity of IHL have yet to be elucidated. The present study used an optimized extraction strategy to obtain sesquiterpene lactones from IHL (the resulting product termed ethyl acetate extract of IHL; EEIHL), and examined the potential mechanisms involved in the anti‑pancreatic cancer activity of EEIHL. Ethanol and ethyl acetate were used to extract sesquiterpene lactones from IHL to give the final product EEIHL. Cell Counting Kit‑8, colony formation and Annexin V/propidium iodide assays were used to detect the anti‑proliferative activity of EEIHL. Cell migration was determined with a wound healing assay. mRNA and protein expression levels were analyzed by reverse transcription‑quantitative polymerase chain reaction and western blot analyses, respectively. It was identified that low concentrations of EEIHL caused CFPAC‑1 cell cycle arrest in the G0/G1 phase, whereas high concentrations of EEIHL induced mitochondria‑dependent apoptosis. In addition, EEIHL could inhibit the phosphorylation of the signal transducer and activator of transcription (STAT)3/AKT pathway, potentially resulting in impeded cell mobility. In conclusion, EEIHL could activate mitochondrial‑dependent apoptosis and inhibit cell migration through the STAT3/AKT pathway in CFPAC-1 cells.

Keywords: Inula helenium L.; pancreatic cancer; cell cycle; apoptosis; signal transducer and activator of transcription 3/AKT pathway.

MeSH terms

  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Chromatography, High Pressure Liquid
  • Humans
  • Inula / chemistry*
  • Magnetic Resonance Spectroscopy
  • Membrane Potential, Mitochondrial / drug effects
  • Pancreatic Neoplasms / metabolism*
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / drug effects*

Substances

  • Plant Extracts
  • STAT3 Transcription Factor
  • Proto-Oncogene Proteins c-akt