Luteolin-regulated MicroRNA-301-3p Targets Caspase-8 and Modulates TRAIL Sensitivity in PANC-1 Cells

Anticancer Res. 2020 Feb;40(2):723-731. doi: 10.21873/anticanres.14003.

Abstract

Background/aim: MicroRNAs (miRNAs) play regulatory roles in pancreatic ductal adenocarcinoma (PDAC). However, it is still required to identify the function of miRNA-301-3p in pancreatic cancer cells.

Materials and methods: Effects of luteolin on cell growth, TRAIL cytotoxicity, and miR-301-3p levels were evaluated. The role of miRNA-301-3p in regulating cell proliferation, target gene expression, and TRAIL cytotoxicity were studied.

Results: The levels of miR-301-3p were down-regulated in PANC-1 cells exposed to luteolin, which inhibits the growth of PANC-1 cells and sensitizes cells to TRAIL. The knockdown of miR-301-3p attenuates cell proliferation and enhances TRAIL cytotoxicity. In addition, caspase-8 was directly targeted by miR-301-3p.

Conclusion: Our findings unveil a critical biological function of miR-301-3p in regulating cell proliferation and elevating an antiproliferative effect of TRAIL on cancer cells. Our observation of miR-301-3p/caspase-8 relationship can also serve to clarify the role of miR-301-3p in other cancer types and related diseases.

Keywords: TRAIL; caspase-8; combination effect; luteolin; miRNA-301-3p; pancreatic cancer.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Carcinoma, Pancreatic Ductal / drug therapy*
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / metabolism*
  • Caspase 8 / genetics
  • Caspase 8 / metabolism*
  • Cell Line, Tumor
  • Down-Regulation / drug effects
  • Drug Synergism
  • Gene Knockdown Techniques
  • Humans
  • Luteolin / administration & dosage
  • Luteolin / pharmacology*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Recombinant Proteins / pharmacology
  • TNF-Related Apoptosis-Inducing Ligand / administration & dosage
  • TNF-Related Apoptosis-Inducing Ligand / pharmacology*
  • Transfection

Substances

  • MIRN301A microRNA, human
  • MicroRNAs
  • Recombinant Proteins
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • CASP8 protein, human
  • Caspase 8
  • Luteolin