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: M Kondoh, T Usui, S Kobayashi, K Tsuchiya, K Nishikawa, T Nishikiori, T Mayumi, H Osada
• Journal: Cancer letters (Cancer Lett) Vol. 126 Issue 1 Pg. 29-32 (Apr 10 1998) ISSN: 0304-3835 [Print] Ireland
• PMID: 9563645 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Pyrones
• pironetin
• Demecolcine

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Cell Cycle (drug effects)
• Cell Division (drug effects)
• Demecolcine (pharmacology)
• Humans
• Mice
• Pyrones (pharmacology)
• Tumor Cells, Cultured