Artemisinin induces A549 cell apoptosis dominantly via a reactive oxygen species-mediated amplification activation loop among caspase-9, -8 and -3

Apoptosis. 2013 Oct;18(10):1201-13. doi: 10.1007/s10495-013-0857-z.

Abstract

This report is designed to explore the roles of caspase-8, -9 and -3 in artemisinin (ARTE)-induced apoptosis in non-small cell lung cancer cells (A549 cells). ARTE induced reactive oxygen species (ROS)-mediated apoptosis in dose- and time-dependent fashion. Although ARTE treatment did not induce Bid cleavage and significant loss of mitochondrial membrane potential, it induced release of Smac and AIF but not cytochrome c from mitochondria, and silencing of Bak but not Bax significantly prevented ARTE-induced cytotoxicity. Moreover, ARTE treatment induced ROS-dependent activation of caspase-9, -8 and -3. Of the utmost importance, silencing or inhibiting any one of caspase-8, -9 and -3 almost completely prevented ARTE-induced activation of all the three caspases and remarkably abrogated the cytotoxicity of ARTE, suggesting that ARTE triggered an amplification activation loop among caspase-9, -8 and -3. Collectively, our data demonstrate that ARTE induces a ROS-mediated amplification activation loop among caspase-9, -8 and -3 to dominantly mediate the apoptosis of A549 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Artemisinins / pharmacology*
  • BH3 Interacting Domain Death Agonist Protein / biosynthesis
  • Caspase 3 / metabolism*
  • Caspase 8 / metabolism*
  • Caspase 9 / metabolism*
  • Cell Line, Tumor
  • Enzyme Activation
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Reactive Oxygen Species / metabolism*

Substances

  • Antineoplastic Agents
  • Artemisinins
  • BH3 Interacting Domain Death Agonist Protein
  • Reactive Oxygen Species
  • artemisinine
  • Caspase 3
  • Caspase 8
  • Caspase 9