CELL-CYCLE ARREST AND ANTITUMOR-ACTIVITY OF PIRONETIN AND ITS DERIVATIVES

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 t he cell proliferation of 3Y1 cells, however, epoxypironetin showed onl y a weak inhibitory activity, The cell cycle analysis revealed that th ese compounds arrested the cell cycle progression at the M-phase in a dose-dependent manner. These antiproliferative effects of pironetin we re also observed in the range 5-25 ng/ml with several tumor cell lines , In CDF1-SLC mice bearing P388 leukemia cells, the intraperitoneal ad ministration of 6.3 mg/kg pironetin over a 5-day period showed a moder ate antitumor effect (T/C, 128%). As the chemical structure of pironet in is different from other M-phase inhibitors such as colchicine or vi nblastine, pironetin will be the lead compound for a potential new ant itumor drug, (C) 1998 Elsevier Science ireland Ltd.