Document Detail


Effects of (5Z)-7-oxozeaenol on MDA-MB-231 breast cancer cells.
MedLine Citation:
PMID:  22753698     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIM: (5Z)-7-Oxozeaenol was studied to reveal the path through which it exerts its effects on triple-negative MDA-MB-231 breast cancer cells.
MATERIALS AND METHODS: The apoptotic effect of (5Z)-7-oxozeaenol on MDA-MB-231 cancer cells was analyzed by cell flow cytometry. The effects of (5Z)-7-oxozeaenol on the expression of the nuclear factor kappa B (NF-κB) p65, p50, IκB kinase (IKKα), IKKβ and caspase-7 were analyzed by western blot. The expression of intracellular reactive oxygen species (ROS) and effects on cell adhesion were also assessed. Cell viability was determined using the 3[4,5-dimethylthiazol-2-yl-]2,5-diphenyl tetrazolium bromide (MTT) assay.
RESULTS: (5Z)-7-Oxozeaenol down-regulated NF-κB in a dose-dependent manner. Intracellular levels of ROS increased in a dose-dependent manner when treated with (5Z)-7-oxozeaenol and potentiated in the presence of H(2)O(2), when compared to paclitaxel which was used as positive control. Treatment with (5Z)-7-oxozeaenol resulted in G1-phase arrest of treated cells and inhibition of cell proliferation. Cell adhesion was notably affected in treated cells. (5Z)-7-Oxozeaenol also significantly enhanced apoptosis of treated cells, through the activation of caspase-7.
CONCLUSION: Our findings suggest that (5Z)-7-oxozeaenol is a potent up-stream inhibitor of the NF-κB pathway, enhances the sensitivity of treated cells to apoptosis induced by ROS, and affects cell adhesion of MDA-MB-231 breast cancer cells. Thus, (5Z)-7-oxozeaenol is a potential new lead for breast cancer drug development since it might, in combination therapy, enhance the efficacy of current treatments and reduce resistance to chemotherapy of triple negative breast cancer.
Authors:
Ulyana Muñoz Acuña; Jennifer Wittwer; Sloan Ayers; Cedric J Pearce; Nicholas H Oberlies; Esperanza J Carcache DE Blanco
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  32     ISSN:  1791-7530     ISO Abbreviation:  Anticancer Res.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-03     Completed Date:  2012-10-08     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  2415-21     Citation Subset:  IM    
Affiliation:
Division of Pharmacy Practice and Administration, College of Phamacy, The Ohio State University, 500 West 12th Avenue, Columbus, OH 43210-1291, USA.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects
Blotting, Western
Breast Neoplasms / drug therapy*,  metabolism,  pathology
Cell Adhesion / drug effects
Cell Cycle / drug effects
Cell Growth Processes / drug effects
Cell Line, Tumor
Cell Survival / drug effects
Estrogens, Non-Steroidal / pharmacology
Female
Flow Cytometry
Humans
NF-kappa B / metabolism
Reactive Oxygen Species / metabolism
Zearalenone / analogs & derivatives*,  pharmacology
Grant Support
ID/Acronym/Agency:
P01 CA125066/CA/NCI NIH HHS; P01 CA125066/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/5-7-oxo-zeaenol; 0/Estrogens, Non-Steroidal; 0/NF-kappa B; 0/Reactive Oxygen Species; 17924-92-4/Zearalenone
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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