Caspase-8 dependent trail-induced apoptosis in cancer cell lines is inhibited by vitamin C and catalase Journal Article
| Authors: | Perez-Cruz, I.; Cárcamo, J. M.; Golde, D. W. |
| Article Title: | Caspase-8 dependent trail-induced apoptosis in cancer cell lines is inhibited by vitamin C and catalase |
| 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. © 2006 Springer Science + Business Media, LLC. |
| Keywords: | controlled study; human cell; neoplasms; drug inhibition; apoptosis; antineoplastic activity; cancer cell culture; enzyme activation; cell line, tumor; cancer resistance; enzyme regulation; drug mechanism; tumor necrosis factor related apoptosis inducing ligand; recombinant proteins; reactive oxygen species; reactive oxygen metabolite; vitamin supplementation; caspase 8; hydrogen peroxide; antioxidant; oxidative stress; ascorbic acid; cell protection; membrane potential, mitochondrial; tnf-related apoptosis-inducing ligand; u937 cells; k562 cells; ros; trail; catalase; caspase-8 |
| Journal Title: | Apoptosis |
| Volume: | 12 |
| Issue: | 1 |
| ISSN: | 1360-8185 |
| Publisher: | Springer |
| Date Published: | 2007-01-01 |
| Start Page: | 225 |
| End Page: | 234 |
| Language: | English |
| DOI: | 10.1007/s10495-006-0475-0 |
| PUBMED: | 17031493 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 27" - "Export Date: 17 November 2011" - "CODEN: APOPF" - "Source: Scopus" |
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