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 β-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 10-6M concentrations of the drugs increased the initial 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 10-5M. 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.
|Published - Jan 1 1980