title: Antiproliferative and Pro-apoptotic Activities of a Novel Resveratrol Prodrug Against Jurkat CD4+ T-Cells.
abstract: OBJECTIVE
  Resveratrol, a natural polyphenol, possesses many beneficial health properties but its therapeutic application is limited due to its low water solubility and instability against oxidative processes. To improve the stability and lipophilicity of the natural compound, we synthesized a resveratrol prodrug, termed FEHH4-1. In the present study, we compared the antiproliferative and pro-apoptotic effects of resveratrol with FEHH4-1 on Jurkat T-cells.
  
  
  METHODS
  Cell proliferation and 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 blot. To induce interleukin-2 (IL2) expression, cells were stimulated with phorbol 12-myristate 13-acetate/phytohemagglutinin. IL2 production was quantified by enzyme-linked immunosorbent assay. IL2 promoter activity was studied by a Jurkat T-cell line containing an IL2 promoter luciferase reporter construct.
  
  
  RESULTS
  Both polyphenols inhibited proliferation, induced apoptotic cell death and blocked IL2 synthesis in Jurkat T-cells. Most importantly, FEHH4-1 was three-to four-times more potent than resveratrol.
  
  
  CONCLUSIONS
  FEHH4-1 had improved antiproliferative and pro-apoptotic potential against Jurkat T-cells compared to resveratrol.
authors: Department of Degenerative Joint Diseases, Ludwig Boltzmann Cluster of Arthritis and Rehabilitation, Vienna, Austria Division of Rheumatology, Department for Internal Medicine III, Medical University Vienna, Vienna, Austria.
authors: Katrin
authors: K
authors: Goldhahn
authors: RD&C Research, Development & Consulting GmbH, Vienna, Austria.
authors: Norbert
authors: N
authors: Handler
authors: Department of Degenerative Joint Diseases, Ludwig Boltzmann Cluster of Arthritis and Rehabilitation, Vienna, Austria.
authors: Silvia
authors: S
authors: Loebsch
authors: Department for Laboratory Medicine, Medical University Vienna, Vienna, Austria.
authors: Klaus
authors: K
authors: Schmetterer
authors: Department of Degenerative Joint Diseases, Ludwig Boltzmann Cluster of Arthritis and Rehabilitation, Vienna, Austria Division of Rheumatology, Department for Internal Medicine III, Medical University Vienna, Vienna, Austria.
authors: Guenter
authors: G
authors: Steiner
authors: Department of Degenerative Joint Diseases, Ludwig Boltzmann Cluster of Arthritis and Rehabilitation, Vienna, Austria burkhard.kloesch@gmx.at.
authors: Burkhard
authors: B
authors: Kloesch
authors: Department for Pharmaceutical Chemistry, University of Vienna, Vienna, Austria.
authors: Thomas
authors: T
authors: Erker
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011355:Prodrugs / Q000138:chemical synthesis / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D000077185:Resveratrol; D013267:Stilbenes / Q000138:chemical synthesis / Q000494:pharmacology*; D014162:Transfection
chemical_list: C000608951:(4-(2-(3,5-bis(ethoxycarbonyloxy)phenyl)vinyl)phenyl) ethyl carbonate; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C508594:IL2 protein, human; D007376:Interleukin-2; D011355:Prodrugs; D013267:Stilbenes; D000077185:Resveratrol
keywords: FEHH4-1; Jurkat CD4+ T-cells; Resveratrol; apoptosis; proliferation