| Enniatin exerts p53-dependent cytostatic and p53-independent cytotoxic activities against human cancer cells. | |
| | |
MedLine Citation:
|
PMID: 17326668 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Worldwide, multiple Fusarium mycotoxins occur as contaminants of cereals with important impacts on human and animal health. The aim of this study was to investigate the effects of the widespread Fusarium secondary metabolite enniatin (ENN), a cyclic hexadepsipeptide, on human cell growth and survival. While short-term exposure (up to 8 h) to ENN at nanomolar concentrations slightly but significantly stimulated cell proliferation, it showed profound apoptosis-inducing effects especially against various human cancer cell types at low micromolar concentrations (already after 24 h of treatment). Several cellular changes indicative for programmed cell death such as cell shrinkage, chromatin condensation, DNA fragmentation, and apoptotic body formation were observed. Correspondingly, the cleavage of poly(ADP-ribosyl)polymerase and the activation of multiple caspases accompanied a distinct loss of mitochondrial membrane potential. To investigate the impact of apoptosis- and cell cycle-regulating proteins on ENN activity, HCT116 cells with homozygously disrupted p53, p21, or bax genes were analyzed. In vitality assays, no significant influences of these proteins on the anticancer activity of ENN were detectable. In contrast, 3H-thymidine incorporation revealed a significantly more efficient block of DNA synthesis in p53 wild-type as compared to knock-out cells. Accordingly, fluorescence-activated cell sorting analysis demonstrated a stronger ENN-induced cell cycle arrest in the G0/G1 phase. Profound ENN-mediated induction of p53 and the p53-downstream cell cycle inhibitor p21 were detectable in p53 wild-type cells by Western blotting. P53-independent p21 induction was also detectable at higher ENN concentrations in p53 (-/-) cells. In contrast, bax activation by ENN was independent of the cellular p53 status. In summary, our results suggest that short-term exposure to very low ENN concentrations, for example, via food intake, might have tumor-promoting functions based on growth stimulation. In contrast, elevated ENN concentrations exert profound p53-dependent cytostatic and p53-independent cytotoxic activities especially against human cancer cells, suggesting a potential quality of ENN as an anticancer drug. |
| | |
Authors:
|
Rita Dornetshuber; Petra Heffeter; Majid-Reza Kamyar; Thomas Peterbauer; Walter Berger; Rosa Lemmens-Gruber |
Related Documents
:
|
9041178 - Expression of wild-type p53 increases etoposide cytotoxicity in m1 myeloid leukemia cel... 9332498 - Egf effects on p53 in mda-468 human breast cancer cells: implications for g1 arrest. 11888918 - Transformed and tumor-derived human cells exhibit preferential sensitivity to the thiol... 12750388 - Tumor suppressor p53 and its homologue p73alpha affect cell migration. 3540508 - Altered metabolism and cell surface expression of glycosphingolipids caused by vitamin ... 6892118 - Uptake of methylmercury and inorganic mercury by mouse glioma and mouse neuroblastoma c... |
Publication Detail:
|
Type: Journal Article Date: 2007-02-28 |
Journal Detail:
|
Title: Chemical research in toxicology Volume: 20 ISSN: 0893-228X ISO Abbreviation: Chem. Res. Toxicol. Publication Date: 2007 Mar |
Date Detail:
|
Created Date: 2007-03-19 Completed Date: 2007-05-21 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8807448 Medline TA: Chem Res Toxicol Country: United States |
Other Details:
|
Languages: eng Pagination: 465-73 Citation Subset: IM |
Affiliation:
|
Department of Pharmacology and Toxicology, University of Vienna, Althanstrasse 14, Vienna, Austria. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Antineoplastic Agents* Apoptosis / drug effects Blotting, Western Caspase 3 / metabolism Caspase 7 / metabolism Cell Cycle / drug effects Cell Cycle Proteins / physiology Cell Survival / drug effects DNA Fragmentation / drug effects Depsipeptides / pharmacology* Fluorescein-5-isothiocyanate Fluorescent Dyes Humans Indoles KB Cells Membrane Potentials / drug effects Mitochondrial Membranes / drug effects Phalloidine Signal Transduction / drug effects Thymidine / metabolism Tumor Suppressor Protein p53 / genetics*, physiology* |
| Chemical | |
Reg. No./Substance:
|
0/Antineoplastic Agents; 0/Cell Cycle Proteins; 0/Depsipeptides; 0/Fluorescent Dyes; 0/Indoles; 0/Tumor Suppressor Protein p53; 0/enniatins; 17466-45-4/Phalloidine; 3326-32-7/Fluorescein-5-isothiocyanate; 47165-04-8/DAPI; 50-89-5/Thymidine; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 7 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Apolipoprotein A-V interaction with members of the low density lipoprotein receptor gene family.
Next Document: Surface forces and drag coefficients of microspheres near a plane surface measured with optical twee...