title: Effects of (5Z)-7-oxozeaenol on MDA-MB-231 breast cancer cells.
abstract: OBJECTIVE
  (5Z)-7-Oxozeaenol was studied to reveal the path through which it exerts its effects on triple-negative MDA-MB-231 breast cancer cells.
  
  
  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.
  
  
  CONCLUSIONS
  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: Division of Pharmacy Practice and Administration, College of Phamacy, The Ohio State University, 500 West 12th Avenue, Columbus, OH 43210-1291, USA.
authors: Ulyana Muñoz
authors: UM
authors: Acuña
authors: Jennifer
authors: J
authors: Wittwer
authors: Sloan
authors: S
authors: Ayers
authors: Cedric J
authors: CJ
authors: Pearce
authors: Nicholas H
authors: NH
authors: Oberlies
authors: Esperanza J Carcache
authors: EJ
authors: DE Blanco
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015025:Zearalenone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000008:administration & dosage; D007783:Lactones; D012118:Resorcinols
chemical_list: D004968:Estrogens, Non-Steroidal; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D015025:Zearalenone; C505734:7-oxozeanol; D007783:Lactones; D012118:Resorcinols