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Comparative Effects of Vindesine, Vinblastine, and Vincristine on Mitotic Arrest and Hormonal Response of L1210 Leukemia Cells¹

Department of Medicine, University of Minnesota Medical School [S. M. H. H., A. T.], and the Dight Institute for Human Genetics [J. R. S.], University of Minnesota, Minneapolis, Minnesota 55455

The Vinca alkaloids vinblastine, vincristine, and vindesine were compared for their capacity to arrest L1210 cells in mitosis and for their effect on the response of L1210 cells to ß-adrenergic and prostaglandin E₁ hormones. Both microscopic and flow cytofluorimetric studies showed that, of the three drugs, vindesine was the most potent for inhibiting growth and arresting L1210 cells in mitosis.

In the hormone response studies, vindesine was also found to be the most potent of the three drugs. Cells pretreated for 30 min with 10^-6 M concentrations of the drugs increased the initial hormone response after 5 min of L1210 cells to either hormone by 100%. After a 1-hr exposure to either isoproterenol or prostaglandin E₁, however, the vindesine-treated cells had cyclic adenosine 3':5'-monophosphate levels several times higher than did controls. Vinblastine- and vincristine-treated cells were not different from the controls after 1 hr of hormone exposure. Dose-response studies show that the vindesine effect on enhanced cyclic adenosine 3':5'-monophosphate accumulation increases substantially with drug concentrations from 10^-8 to 10^-5 M. These and other studies indicate that the effect of the Vinca alkaloids on cyclic adenosine 3':5'-monophosphate metabolism occurs at the transduction mechanism which couples the hormone receptor to the catalytic component of the adenylate cyclase complex.

¹ Supported by Grants CA-19527 from the NIH, the Minnesota Medical Foundation, and the Leukemia Task Force.

² To whom requests for reprints should be addressed.

Received 1/21/80. Accepted 4/29/80.