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Research Article

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

ULYANA MUÑOZ ACUÑA, JENNIFER WITTWER, SLOAN AYERS, CEDRIC J. PEARCE, NICHOLAS H. OBERLIES and ESPERANZA J. CARCACHE DE BLANCO
Anticancer Research July 2012, 32 (7) 2415-2421;
ULYANA MUÑOZ ACUÑA
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JENNIFER WITTWER
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SLOAN AYERS
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CEDRIC J. PEARCE
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NICHOLAS H. OBERLIES
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ESPERANZA J. CARCACHE DE BLANCO
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  • For correspondence: carcache@pharmacy.ohio-state.edu
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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-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 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-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.

  • (5Z)-7-Oxozeaenol
  • MDA-MB-231
  • NF-κB
  • caspase-7
  • apoptosis
  • IKK
  • ROS
  • Received April 17, 2012.
  • Revision received June 11, 2012.
  • Accepted June 12, 2012.
  • Copyright© 2012 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
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Anticancer Research: 32 (7)
Anticancer Research
Vol. 32, Issue 7
July 2012
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Effects of (5Z)-7-Oxozeaenol on MDA-MB-231 Breast Cancer Cells
ULYANA MUÑOZ ACUÑA, JENNIFER WITTWER, SLOAN AYERS, CEDRIC J. PEARCE, NICHOLAS H. OBERLIES, ESPERANZA J. CARCACHE DE BLANCO
Anticancer Research Jul 2012, 32 (7) 2415-2421;

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Effects of (5Z)-7-Oxozeaenol on MDA-MB-231 Breast Cancer Cells
ULYANA MUÑOZ ACUÑA, JENNIFER WITTWER, SLOAN AYERS, CEDRIC J. PEARCE, NICHOLAS H. OBERLIES, ESPERANZA J. CARCACHE DE BLANCO
Anticancer Research Jul 2012, 32 (7) 2415-2421;
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