title: Effects of (5Z)-7-oxozeaenol on the oxidative pathway of cancer cells.
abstract: OBJECTIVE
  As part of an on going investigation of novel anticancer agents from natural origin, the biological and cellular effects of (5Z)-7-oxozeaenol on cancer cells were investigated.
  
  
  METHODS
  The expression of nuclear factor kappa B (NF-κB), IκB kinase (IKKα), IKKβ and caspase-3 were analyzed by western blot. Reactive oxygen species (ROS) fluorescence and caspase luminescent assays were used to assess the intracellular effects in HeLa cervical and HT-29 colon cancer cell lines. The mitochondrial transmembrane potential (MTP) was analyzed by fluorescence-activated cell sorting (FACS).
  
  
  RESULTS
  Cells treated with (5Z)-7-oxozeaenol exhibited down-regulation of NF-κB in a dose-dependent manner. Treatment with (5Z)-7-oxozeaenol significantly enhanced the levels of ROS in HeLa and HT-29 cells. MTP was reduced in HT-29 cells. The expression of caspase-3 and -7 was induced in (5Z)-7-oxozeaenol treated HeLa cells, in comparison with those treated with paclitaxel.
  
  
  CONCLUSIONS
  Our findings suggest that (5Z)-7-oxozeaenol is a potent inhibitor of the NF-κB pathway and potentiates the production of ROS, as well as induces caspase-3 and -7 in HeLa and HT-29 cancer cells. Thus, (5Z)-7-oxozeaenol represents a new lead compound for drug development, particularly as a new cancer chemotherapeutic agent, since programmed cell death might be mediated through the activation of a caspase-arbitrated pathway.
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: D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D015025:Zearalenone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000008:administration & dosage; D007783:Lactones; D012118:Resorcinols
chemical_list: D053148:Caspase 3; D053179:Caspase 7; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D015025:Zearalenone; C505734:7-oxozeanol; D007783:Lactones; D012118:Resorcinols