title: Enhanced Antiproliferative and Pro-apoptotic Activities of a Novel Curcumin-related Compound in Jurkat Leukemia T-Cells.
abstract: OBJECTIVE
  Inhibition of arachidonic acid metabolism by curcumin has been suggested to be a key mechanism for its anti-carcinogenic action. Recently, we reported on the synthesis of curcumin analogues and their evaluation as selective COX1 inhibitors. Two compounds (HP109/HP102) were selected for evaluation of their anti-proliferative and pro-apoptotic potential in Jurkat T-cells.
  
  
  METHODS
  Jurkat T-cells were stimulated with phorbol 12-myristate 13-acetate/phytohemagglutinin (PMA/PHA) in the absence and presence of different concentrations of curcumin or HP109/HP102. Interleukin 2 (IL2) production and IL2 promoter activity were analyzed by enzyme-linked immunosorbent assay and a luciferase reporter assay, respectively. Proliferation and cell viability were monitored by 2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2H-Tetrazolium-5-Carboxanilide assay, annexin -V/7-amino-actinomycin D staining and western blotting.
  
  
  RESULTS
  HP102 was about 10-times more effective in blocking IL2 synthesis compared to curcumin. Enhanced effects of HP102 were also observed in reducing the proliferation rate and cell viability. In contrast to HP102, HP109 did not exhibit enhanced effects compared to curcumin.
  
  
  CONCLUSIONS
  The curcumin analog HP102 had strongly improved the anti-proliferative and pro-apoptotic potential in Jurkat T-cells compared to curcumin.
authors.affiliation: Ludwig Boltzmann Institute for Rheumatology and Balneology, Cluster Rheumatology, Balneology and Rehabilitation, Vienna, Austria.
authors.forename: Katrin
authors.initials: K
authors.lastname: Goldhahn
authors.affiliation: Division of Drug Design and Medicinal Chemistry, Department of Pharmaceutical Chemistry, University of Vienna, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Hintersteininger
authors.affiliation: Ludwig Boltzmann Institute for Rheumatology and Balneology, Cluster Rheumatology, Balneology and Rehabilitation, Vienna, Austria Division of Rheumatology, Department of Internal Medicine III, Medical University Vienna, Vienna, Austria.
authors.forename: Guenter
authors.initials: G
authors.lastname: Steiner
authors.affiliation: Division of Drug Design and Medicinal Chemistry, Department of Pharmaceutical Chemistry, University of Vienna, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Erker
authors.affiliation: Ludwig Boltzmann Institute for Rheumatology and Balneology, Cluster Rheumatology, Balneology and Rehabilitation, Vienna, Austria burkhard.kloesch@gmx.at.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Kloesch
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D003474:Curcumin / Q000008:administration & dosage* / Q000031:analogs & derivatives; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000473:pathology
chemical_list: D007376:Interleukin-2; D003474:Curcumin
keywords: Curcumin; HP102; IL2; Jurkat T-cells; apoptosis; proliferation