Arctigenin enhances chemosensitivity to cisplatin in human nonsmall lung cancer H460 cells through downregulation of survivin expression

J Biochem Mol Toxicol. 2014 Jan;28(1):39-45. doi: 10.1002/jbt.21533. Epub 2013 Nov 8.

Abstract

Arctigenin, a dibenzylbutyrolactone lignan, enhances cisplatin-mediated cell apoptosis in cancer cells. Here, we sought to investigate the effects of arctigenin on cisplatin-treated non-small-cell lung cancer (NSCLC) H460 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and annexin-V/propidium iodide staining were performed to analyze the proliferation and apoptosis of H460 cells. Arctigenin dose-dependently suppressed cell proliferation and potentiated cell apoptosis, coupled with increased cleavage of caspase-3 and poly(ADP-ribose) polymerase. Moreover, arctigenin sensitized H460 cells to cisplatin-induced proliferation inhibition and apoptosis. Arctigenin alone or in combination with cisplatin had a significantly lower amount of survivin. Ectopic expression of survivin decreased cell apoptosis induced by arctigenin (P < 0.05) or in combination with cisplatin (P < 0.01). Moreover, arctigenin (P < 0.05) or in combination with cisplatin (P < 0.01) induced G1/G0 cell-cycle arrest. Our data provide evidence that arctigenin has a therapeutic potential in combina-tion with chemotherapeutic agents for NSLC.

Keywords: Apoptosis; Arctigenin; Chemoresistance; Cisplatin; Non-small-cell lung cancer (NSCLC).

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Base Sequence
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Cycle
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • DNA Primers
  • Down-Regulation / drug effects*
  • Drug Resistance, Neoplasm
  • Drug Synergism
  • Furans / pharmacology*
  • Humans
  • Inhibitor of Apoptosis Proteins / metabolism*
  • Lignans / pharmacology*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Polymerase Chain Reaction
  • Survivin

Substances

  • Antineoplastic Agents
  • BIRC5 protein, human
  • DNA Primers
  • Furans
  • Inhibitor of Apoptosis Proteins
  • Lignans
  • Survivin
  • Cisplatin
  • arctigenin