The role of calcium, P38 MAPK in dihydroartemisinin-induced apoptosis of lung cancer PC-14 cells

Cancer Chemother Pharmacol. 2008 Apr;61(4):639-45. doi: 10.1007/s00280-007-0517-5. Epub 2007 Jul 4.

Abstract

Introduction: Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin isolated from the traditional Chinese herb Artemisia annua, is an effective novel antimalarial drug. Recent studies suggest that it also has anticancer effect.

Purpose: The present study was designed to investigate the effects of DHA on cultured human lung cancer cells (PC-14 cells) to better understand its apoptosis and apoptosis-related factors in vitro.

Methods: The cell viability was measured by MTT assay. The apoptosis induction was examined by DNA ladder and flow cytometry. The intracellular-free calcium concentration in the lung cancer cells were evaluated by laser scanning confocal microscopy with Fura-3/AM as probe. The associated gene expression was examined by Western blot.

Results: After treatment with DHA, a decrease in the viability of PC-14 cells and apoptosis were observed. DHA-induced apoptosis were accompanied by an increase of Ca(2+) and activation of p38. Deleted levels of Ca(2+) by BAPTA-AM 20 microM or inhibition of p38 by its selective inhibitor SB202190 then led to decreased DHA-induced apoptosis.

Conclusions: These results demonstrated that DHA can induce apoptosis of lung cancer cell line PC-14 cells and calcium and p38 play important roles in the apoptotic signalling pathways.

MeSH terms

  • Antimalarials / pharmacology*
  • Apoptosis / drug effects
  • Artemisinins / pharmacology*
  • Blotting, Western
  • Calcium / metabolism
  • Calcium / physiology*
  • Cell Line, Tumor
  • Chelating Agents / pharmacology
  • DNA Fragmentation / drug effects
  • DNA, Neoplasm / biosynthesis
  • DNA, Neoplasm / genetics
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Flow Cytometry
  • Fluorescent Dyes
  • Humans
  • Imidazoles / pharmacology
  • Lung Neoplasms / pathology*
  • Pyridines / pharmacology
  • Sesquiterpenes / pharmacology*
  • Tetrazolium Salts
  • Thiazoles
  • p38 Mitogen-Activated Protein Kinases / physiology*

Substances

  • Antimalarials
  • Artemisinins
  • Chelating Agents
  • DNA, Neoplasm
  • Enzyme Inhibitors
  • Fluorescent Dyes
  • Imidazoles
  • Pyridines
  • Sesquiterpenes
  • Tetrazolium Salts
  • Thiazoles
  • 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
  • Egtazic Acid
  • artenimol
  • p38 Mitogen-Activated Protein Kinases
  • thiazolyl blue
  • 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole
  • Calcium