Apoptosis

, 12:225 | Cite as

Caspase-8 dependent trail-induced apoptosis in cancer cell lines is inhibited by vitamin C and catalase

  • Isabel Perez-Cruz
  • Juan M. Cárcamo
  • David W. Golde
Article

Abstract

TNF-related apoptosis-inducing ligand (TRAIL/ Apo-2L) is a member of the TNF family of apoptosis-inducing proteins that initiates apoptosis in a variety of neoplastic cells while displaying minimal or absent cytotoxicity to most normal cells. Therefore, TRAIL is currently considered a promising target to develop anti-cancer therapies. TRAIL-receptor ligation recruits and activates pro-caspase-8, which in turn activates proteins that mediate disruption of the mitochondrial membranes. These events lead to the nuclear and cytosolic damage characteristic of apoptosis. Here we report that TRAIL-induced apoptosis is mediated by oxidative stress and that vitamin C (ascorbic acid), a potent nutritional antioxidant, protects cancer cell lines from apoptosis induced by TRAIL. Vitamin C impedes the elevation of reactive oxygen species (ROS) levels induced by TRAIL and impairs caspase-8 activation. We found that the removal of hydrogen peroxide by extracellular catalase during TRAIL-induced apoptosis also impairs caspase-8 activation. These data suggest that hydrogen peroxide is produced during TRAIL-receptor ligation, and that the increase of intracellular ROS regulates the activation of caspase-8 during apoptosis. Additionally we propose a mechanism by which cancer cells might resist apoptosis via TRAIL, by the intake of the nutritional antioxidant vitamin C.

Keywords

TRAIL Apoptosis Ascorbic acid Caspase-8 Catalase ROS Hydrogen peroxide 

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Copyright information

© Springer Science + Business Media, LLC 2006

Authors and Affiliations

  • Isabel Perez-Cruz
    • 1
    • 4
  • Juan M. Cárcamo
    • 1
    • 2
    • 3
  • David W. Golde
    • 1
  1. 1.Program in Molecular Pharmacology and ChemistryMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  2. 2.Department of Clinical LaboratoriesMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  3. 3.Enzo Life SciencesNew York
  4. 4.New York University Cancer CenterNew YorkUSA

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