title: Cell cycle arrest and antitumor activity of pironetin and its derivatives.
abstract: The biological effects of pironetin and its derivatives on cell cycle progression and antitumor activity were studied. At 10-20 ng/ml, both pironetin and its demethyl derivative, NK10958P completely inhibited the cell proliferation of 3Y1 cells, however, epoxypironetin showed only a weak inhibitory activity. The cell cycle analysis revealed that these compounds arrested the cell cycle progression at the M-phase in a dose-dependent manner. These antiproliferative effects of pironetin were also observed in the range 5-25 ng/ml with several tumor cell lines. In CDF1-SLC mice bearing P388 leukemia cells, the intraperitoneal administration of 6.3 mg/kg pironetin over a 5-day period showed a moderate antitumor effect (T/C, 128%). As the chemical structure of pironetin is different from other M-phase inhibitors such as colchicine or vinblastine, pironetin will be the lead compound for a potential new antitumor drug.
authors.affiliation: The Institute of Physical and Chemical Research (RIKEN), Saitama, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kondoh
authors.forename: T
authors.initials: T
authors.lastname: Usui
authors.forename: S
authors.initials: S
authors.lastname: Kobayashi
authors.forename: K
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: K
authors.initials: K
authors.lastname: Nishikawa
authors.forename: T
authors.initials: T
authors.lastname: Nishikiori
authors.forename: T
authors.initials: T
authors.lastname: Mayumi
authors.forename: H
authors.initials: H
authors.lastname: Osada
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D003703:Demecolcine / Q000494:pharmacology; D006801:Humans; D051379:Mice; D011753:Pyrones / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D011753:Pyrones; C088446:pironetin; D003703:Demecolcine