title: A novel curcumin-like dienone induces apoptosis in triple-negative breast cancer cells.
abstract: OBJECTIVE
  According to the World Health Organization (WHO), breast cancer is the most common cancer affecting women worldwide. In the USA ~12.3 % of all women are expected to be diagnosed with various types of breast cancer, exhibiting varying degrees of therapeutic response rates. Therefore, the identification of novel anti-breast cancer drugs is of paramount importance.
  
  
  METHODS
  The 1,5-diaryl-3-oxo-1,4-pentadienyl pharmacophore was incorporated into a number of cytotoxins. Three of the resulting dienones, 2a, 2b and 2c, were tested for their anti-neoplastic potencies in a variety of human breast cancer-derived cell lines, including the triple negative MDA-MB-231 cell line and its metastatic variant, using a live-cell bio-imaging method. Special emphasis was put on dienone 2c, since its anti-cancer activity and its mode of inflicting cell death have so far not been reported.
  
  
  RESULTS
  We found that all three dienones exhibited potent cytotoxicities towards the breast cancer-derived cell lines tested, whereas significantly lower toxicities were observed towards the non-cancerous human breast cell line MCF-10A. The dienones 2b and 2c exhibited the greatest selective cytotoxicity at submicromolar concentration levels. We found that these two dienones induced phosphatidylserine externalization in MDA-MB-231 cells in a concentration-dependent manner, suggesting that their cytotoxic effect might be mediated by apoptosis. This possibility was confirmed by our observation that the dienone 2c can induce mitochondrial depolarization, caspase-3 activation, cell cycle disruption and DNA fragmentation in MDA-MB-231 cells.
  
  
  CONCLUSIONS
  Our findings indicate that dienone 2c uses the mitochondrial/intrinsic pathway to inflict apoptosis in triple negative MDA-MB-231 breast cancer-derived cells. This observation warrants further assessment of dienone 2c as a potential anti-breast cancer drug.
authors.affiliation: Cytometry, Screening and Imaging Core Facility, Border Biomedical Research Center, Department of Biological Sciences, the University of Texas at El Paso, 500 West University Avenue, El Paso, TX, 79968-0519, USA.
authors.forename: Elisa
authors.initials: E
authors.lastname: Robles-Escajeda
authors.affiliation: Drug Discovery & Development Research Group, College of Pharmacy & Nutrition, University of Saskatchewan, 110 Science Place, Saskatoon, SK, S7N 5C9, Canada.
authors.forename: Umashankar
authors.initials: U
authors.lastname: Das
authors.affiliation: Cytometry, Screening and Imaging Core Facility, Border Biomedical Research Center, Department of Biological Sciences, the University of Texas at El Paso, 500 West University Avenue, El Paso, TX, 79968-0519, USA.
authors.forename: Nora M
authors.initials: NM
authors.lastname: Ortega
authors.affiliation: Cytometry, Screening and Imaging Core Facility, Border Biomedical Research Center, Department of Biological Sciences, the University of Texas at El Paso, 500 West University Avenue, El Paso, TX, 79968-0519, USA.
authors.forename: Karla
authors.initials: K
authors.lastname: Parra
authors.affiliation: Cytometry, Screening and Imaging Core Facility, Border Biomedical Research Center, Department of Biological Sciences, the University of Texas at El Paso, 500 West University Avenue, El Paso, TX, 79968-0519, USA.
authors.forename: Giulio
authors.initials: G
authors.lastname: Francia
authors.affiliation: Drug Discovery & Development Research Group, College of Pharmacy & Nutrition, University of Saskatchewan, 110 Science Place, Saskatoon, SK, S7N 5C9, Canada.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Dimmock
authors.affiliation: Cytometry, Screening and Imaging Core Facility, Border Biomedical Research Center, Department of Biological Sciences, the University of Texas at El Paso, 500 West University Avenue, El Paso, TX, 79968-0519, USA. avarela2@utep.edu.
authors.forename: Armando
authors.initials: A
authors.lastname: Varela-Ramirez
authors.affiliation: Cytometry, Screening and Imaging Core Facility, Border Biomedical Research Center, Department of Biological Sciences, the University of Texas at El Paso, 500 West University Avenue, El Paso, TX, 79968-0519, USA. raguilera@utep.edu.
authors.forename: Renato J
authors.initials: RJ
authors.lastname: Aguilera
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D003474:Curcumin / Q000031:analogs & derivatives*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D064726:Triple Negative Breast Neoplasms
chemical_list: D000970:Antineoplastic Agents; D003474:Curcumin
keywords: Anti-cancer drug discovery; Apoptosis; Caspase-3; Cell cycle; Curcumin analogues; DNA fragmentation; Mitochondrial depolarization