Calyxin Y induces hydrogen peroxide-dependent autophagy and apoptosis via JNK activation in human non-small cell lung cancer NCI-H460 cells

Cancer Lett. 2013 Oct 28;340(1):51-62. doi: 10.1016/j.canlet.2013.06.021. Epub 2013 Jun 27.

Abstract

Calyxin Y has been recently isolated from Alpinia katsumadai which has a folk use as an anti-tumor medicine. Calyxin Y induced caspase-dependent cell death in NCI-H460 cells, and concomitantly, provoked cytoprotective autophagy with the upregulation of critical Atg proteins. The cleavage of Atg proteins by caspases acted as a switch between autophagy and apoptosis induced by calyxin Y. Intracellular hydrogen peroxide (H2O2) production was triggered upon exposure to calyxin Y via the induction of autophagy and apoptosis. We provided evidence that activated JNK was upstream effectors controlling both autophagy and apoptosis in response to elevated H2O2. Therefore, our findings demonstrate that calyxin Y serves multiple roles as a promising chemotherapeutic agent that induces H2O2-dependent autophagy and apoptosis via JNK activation.

Keywords: 2′,7′-dichlorofluorescein-diacetate; Apoptosis; Atg; Atgs; Autophagy; BCA; BSA; Calyxin Y; DCF; DCFH-DA; ECL; ERK; JNK; LC3; MAPK; PI; ROS; SDS–PAGE; TBST; autophagy related genes; bicinchoninic acid; c-Jun N-terminal protein kinases; dichlorofluorescein; enhanced chemiluminescence; extracellular signal-regulated kinases; fetal bovine serum albumin; microtubule-associated protein1 light chain 3; mitogen-activated protein kinase; propidium iodide; reactive oxygen species; sodium dodecyl sulfate–polyacrylamide gel electrophoresis; tris-buffered saline containing 0.1% Tween-20.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Autophagy / drug effects*
  • Autophagy-Related Protein 12
  • Autophagy-Related Protein 5
  • Carcinoma, Non-Small-Cell Lung
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chalcones / pharmacology*
  • DNA Fragmentation
  • Diarylheptanoids / pharmacology*
  • Enzyme Activation
  • Humans
  • Hydrogen Peroxide / metabolism*
  • Inhibitory Concentration 50
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Microtubule-Associated Proteins / metabolism
  • Small Ubiquitin-Related Modifier Proteins / metabolism
  • Up-Regulation

Substances

  • ATG12 protein, human
  • ATG5 protein, human
  • Antineoplastic Agents, Phytogenic
  • Autophagy-Related Protein 12
  • Autophagy-Related Protein 5
  • Chalcones
  • Diarylheptanoids
  • MAP1LC3A protein, human
  • Microtubule-Associated Proteins
  • Small Ubiquitin-Related Modifier Proteins
  • calyxin Y
  • Hydrogen Peroxide
  • JNK Mitogen-Activated Protein Kinases
  • Caspases