| The thioredoxin system mediates redox-induced cell death in human colon cancer cells: implications for the mechanism of action of anticancer agents. | |
| | |
MedLine Citation:
|
PMID: 18922898 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Anticancer agents act, at least in part, by inducing reactive oxygen and nitrogen species (RONS). We examined the redox effect on SW480 and HT-29 colon cancer cells of four anticancer compounds, arsenic trioxide, phosphoaspirin, phosphosulindac, and nitric oxide-donating aspirin (NO-ASA). All compounds inhibited the growth of both cell lines (IC(50), 10-90 micromol/L) and induced RONS detected by a general RONS molecular probe. NO-ASA, which induced at least four individual RONS (NO, H(2)O(2), superoxide anion, and peroxynitirte), induced apoptotic and necrotic cell death that was RONS-mediated (cell death paralleled RONS levels and was abrogated by N-acetyl cysteine but not by diphenylene iodonium, which displayed prooxidant activity and enhanced cell death). Nuclear factor-kappaB and mitogen-activated protein kinases were modulated by RONS. Thioredoxin-1 (Trx-1), an oxidoreductase involved in redox regulation, was heavily oxidized in response to RONS and mediated the growth inhibitory effect of the anticancer agents; knocking-down trx-1 expression by small interfering RNA abrogated cell death induced by them. These compounds also inhibited the activity of Trx reductase that reduces oxidized Trx-1, whereas the Trx reductase inhibitor aurothiomalate synergized with NO-ASA in the induction of cell death. Our findings indicate that the Trx system mediates to a large extent redox-induced cell death in response to anticancer agents. This mechanism of action may be shared by more anticancer agents and deserves further assessment as a candidate mechanism for the pharmacologic control of cancer. |
| | |
Authors:
|
Yu Sun; Basil Rigas |
Related Documents
:
|
12728248 - Deltafosb, but not fosb, induces delayed apoptosis independent of cell proliferation in... 9144178 - Dad1, the defender against apoptotic cell death, is a subunit of the mammalian oligosac... 21054128 - Comparative study of photothermolysis of cancer cells with nuclear-targeted or cytoplas... 15900708 - Hid can induce, but is not required for autophagy in polyploid larval drosophila tissues. 1825838 - Translocation of cd45ra in neutrophils. 8496158 - Mannosamine inhibits the synthesis of putative glycoinositol phospholipid anchor precur... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Cancer research Volume: 68 ISSN: 1538-7445 ISO Abbreviation: Cancer Res. Publication Date: 2008 Oct |
Date Detail:
|
Created Date: 2008-10-16 Completed Date: 2008-11-07 Revised Date: 2013-04-18 |
Medline Journal Info:
|
Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: United States |
Other Details:
|
Languages: eng Pagination: 8269-77 Citation Subset: IM |
Affiliation:
|
Department of Medicine, Division of Cancer Prevention, Stony Brook University, Stony Brook, New York 11794-5200, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Antineoplastic Agents
/
pharmacology* Apoptosis / drug effects* Arsenicals / pharmacology Aspirin / analogs & derivatives, pharmacology Gold Sodium Thiomalate / pharmacology HT29 Cells Humans MAP Kinase Kinase Kinase 5 / physiology Mitogen-Activated Protein Kinases / metabolism NF-kappa B / metabolism Nitric Oxide Donors / pharmacology Organophosphates / pharmacology Oxidation-Reduction Oxidative Stress Oxides / pharmacology Reactive Nitrogen Species / metabolism Reactive Oxygen Species / metabolism Thioredoxin-Disulfide Reductase / antagonists & inhibitors Thioredoxins / physiology* |
| Grant Support | |
ID/Acronym/Agency:
|
R01 CA092423/CA/NCI NIH HHS; R01 CA092423/CA/NCI NIH HHS; R01 CA101019/CA/NCI NIH HHS; R01 CA10101902/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Antineoplastic Agents; 0/Arsenicals; 0/NF-kappa B; 0/Nitric Oxide Donors; 0/Organophosphates; 0/Oxides; 0/Reactive Nitrogen Species; 0/Reactive Oxygen Species; 0/phosphoaspirin; 12244-57-4/Gold Sodium Thiomalate; 1327-53-3/arsenic trioxide; 50-78-2/Aspirin; 52500-60-4/Thioredoxins; EC 1.8.1.9/Thioredoxin-Disulfide Reductase; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 2.7.11.25/MAP Kinase Kinase Kinase 5; EC 2.7.11.25/MAP3K5 protein, human |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Transient nutlin-3a treatment promotes endoreduplication and the generation of therapy-resistant tet...
Next Document: Arsenic exposure in utero exacerbates skin cancer response in adulthood with contemporaneous distort...