Effects of (5z)-7-Oxozeaenol on MDA-MB-231 Breast Cancer Cells

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Nicholas Oberlies, Patricia A. Sullivan Distinguished Professor of Chemistry (Creator)
Cedric J Pearce, Adjunct Professor (Creator)
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/

Abstract: 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-?B) p65, p50, I?B kinase (IKKa), IKKß 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-?B 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 H2O2, 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-?B 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.

Additional Information

Anticancer Research, 32 (7), 2415-2421
Language: English
Date: 2012
(5Z)-7-Oxozeaenol, MDA-MB-231, NF-?B, caspase-7, apoptosis, IKK, ROS

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