title: Tumor-selective cytotoxicity of a novel pentadiene analogue on human leukemia/ lymphoma cells.
abstract: BACKGROUND
  A novel series of structurally divergent 1,5-diaryl-3-oxo-1,4-pentadiene analogues1-10displayed marked cytotoxic potencies towards a number of human leukemia/lymphoma cells.
  
  
  OBJECTIVE
  To identify novel selective cytotoxic compounds that induce apoptosis.
  
  
  METHODS
  The Differential Nuclear Staining (DNS) screening protocol was utilized to measure the cytotoxicity of all experimental dienones on several cancerous cells. Additionally, the selective cytotoxicity index was calculated by comparing the dienone's cytotoxicity between leukemia/lymphoma cells vs. non-cancerous cells. Furthermore, to discern whether a selected dienone induced cell deathviaapoptosis or necrosis on T-lymphocyte leukemia cells, diverse approaches were utilized to detect individual biochemical facets of apoptosis.
  
  
  RESULTS
  The dienones were tested for their anti-neoplastic efficiency on human leukemia/lymphoma-derived cell lines. Special emphasis was applied on dienone1, on the basis of its sub-micromolar cytotoxicity (CC50=0.43+0.02 μM) and high selective cytotoxicity index (11.1) exerted on T-leukemia cells. In general, dienone1showed the most potent cytotoxic properties as compared to other dienones and a related reference cytotoxin curcumin as well as the EF-24 curcumin analogue. Dienone1caused cell death by apoptosis in Jurkat cells as evidenced by inducing phosphatidylserine externalization, mitochondrial depolarization and caspase-3/7. These effects were mainly attributed to the induction of apoptotic pathways.
  
  
  CONCLUSIONS
  The novel dienone1was found to exhibit potent anti-leukemia activity by inducing programmed cell death/apoptosis. Consequently, dionone1should be developed further to examine its potential efficacy to combat malignancies in a pre-clinical animal model.
authors.affiliation: Department of Biological Sciences, Bioscience Research Building, Border Biomedical Research Center, Cytometry, Screening and Imaging Core Facility, University of Texas at El Paso, Texas, 79968, USA.
authors.forename: Yahaira
authors.initials: Y
authors.lastname: Santiago-Vázquez
authors.affiliation: College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 5C9, Canada.
authors.forename: Umashankar
authors.initials: U
authors.lastname: Das
authors.affiliation: Department of Biological Sciences, Bioscience Research Building, Border Biomedical Research Center, Cytometry, Screening and Imaging Core Facility, University of Texas at El Paso, Texas, 79968, USA.
authors.forename: Armando
authors.initials: A
authors.lastname: Varela-Ramirez
authors.affiliation: Department of Biological Sciences, Bioscience Research Building, Border Biomedical Research Center, Cytometry, Screening and Imaging Core Facility, University of Texas at El Paso, Texas, 79968, USA.
authors.forename: Sarah T
authors.initials: ST
authors.lastname: Baca
authors.affiliation: Department of Biological Sciences, Bioscience Research Building, Border Biomedical Research Center, Cytometry, Screening and Imaging Core Facility, University of Texas at El Paso, Texas, 79968, USA.
authors.forename: Yoshira
authors.initials: Y
authors.lastname: Ayala-Marin
authors.affiliation: Department of Biological Sciences, Bioscience Research Building, Border Biomedical Research Center, Cytometry, Screening and Imaging Core Facility, University of Texas at El Paso, Texas, 79968, USA; College of Optometry, University of Houston, 4901 Calhoun Road, Houston, TX, 77204, USA.
authors.forename: Carolina
authors.initials: C
authors.lastname: Lema
authors.affiliation: College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 5C9, Canada.
authors.forename: Swagatika
authors.initials: S
authors.lastname: Das
authors.affiliation: College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 5C9, Canada.
authors.forename: Alaa
authors.initials: A
authors.lastname: Baryyan
authors.affiliation: College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 5C9, Canada.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Dimmock
authors.affiliation: Department of Biological Sciences, Bioscience Research Building, Border Biomedical Research Center, Cytometry, Screening and Imaging Core Facility, University of Texas at El Paso, Texas, 79968, USA.
authors.forename: Renato J
authors.initials: RJ
authors.lastname: Aguilera
keywords: Apoptosis; Cancer; Caspase 3; Curcumin analogue; Cytotoxins; Leukemia; Mitochondria