title: A novel iodomethylene-dimethyl-dihydropyranone induces G2/M arrest and apoptosis in human cancer cells.
abstract: BACKGROUND
  The putative pharmacophore of a naturally cytotoxic limonoid haperforin B1, E-5-iodomethylene-6,6-dimethyl-5,6-dihydropyran-2-one (IDDP) was synthesized and its biological activity was investigated.
  
  
  METHODS
  The cytotoxicity of IDDP was assessed using human breast, lung, colorectal and epidermal carcinomas, chronic myeloid leukemia and glioblastoma cell lines. Cell cycle analysis was performed by flow cytometry. The induction of apoptosis was studied by a caspase assay and by annexin V-propidium iodide double staining. The organization of actin and tubulin microfilaments was analysed by immunocytochemical labeling.
  
  
  RESULTS
  IDDP was shown to inhibit the growth of a panel of human cancer cell lines independently of their p53 status with IC(50) ranging from 0.07 to 0.50 microM. All the treated cells were arrested in the G(2)/M phase in a time-dependent manner before cell death occurred through an apoptotic pathway. Immunocytochemical studies revealed that the normal organization of microfilaments and microtubules was disrupted in IDDP exposed cells.
  
  
  CONCLUSIONS
  IDDP can be considered as a promising anticancer agent.
authors.affiliation: Institut de Chimie des Substances Naturelles, Centre National de la Recherche Scientifique, 91190 Gif-sur-Yvette, France. Jerome.Bignon@icsn.cnrs-gif.fr
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bignon
authors.forename: Michel
authors.initials: M
authors.lastname: Bénéchie
authors.forename: Denyse
authors.initials: D
authors.lastname: Herlem
authors.forename: Jian-Miao
authors.initials: JM
authors.lastname: Liu
authors.forename: Alexia
authors.initials: A
authors.lastname: Pinault
authors.forename: Françoise
authors.initials: F
authors.lastname: Khuong-Huu
authors.forename: Joanna
authors.initials: J
authors.lastname: Wdzieczak-Bakala
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D016195:G2 Phase / Q000187:drug effects*; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011753:Pyrones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; C543671:E-5-iodomethylene-6,6-dimethyl-5,6-dihydropyran-2-one; D011753:Pyrones