COMPARISON OF THE EFFECTS OF VINBLASTINE, VINCRISTINE, VINDESINE, AND VINEPIDINE ON MICROTUBULE DYNAMICS AND CELL-PROLIFERATION INVITRO

  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (6) , 2741-2747
Abstract
Vinepidine, a new derivative of vincristine and 3 clinically used Catharanthus derivatives, vinblastine, vincristine and vindesine, were examined for their abilities to inhibit net tubulin addition at the assembly ends of bovine brain microtubules at steady-state. Although all 4 derivatives were generally similar in potency, their relative abilities to inhibit tubulin addition were distinguishable. Vinepidine and vincristine were the most potent derivatives (Ki, 0.079 .+-. 0.018 (SD) .mu.M and 0.085 .+-. 0.013 .mu.M, respectively), followed by vindesine (K 0.110 .+-. 0.007 .mu.M) and vinblastine (Ki 0.178 .+-. 0.025 .mu.M). In contrast to their relative abilities to inhibit microtubule assembly in vitro, vinblastine and its derivative, vindesine, were generally more potent than vincristine and vinepidine in inhibiting cell proliferation in culture. Vinblastine was 9 times more potent than the weakest derivative, in B16 melanoma cells. In L-cells, vinblastine completely inhibited growth at 40 nM, whereas vincristine and vindesine caused about 25% inhibition and vinepidine was inactive. When B16 melanoma cells were treated with drug before being injected into mice, retardation of tumor growth was best achieved with vindesine, 1 of the weaker of the 4 derivatives in vitro. The results demonstrate that chemical differences among the Catharanthus derivatives, which affect to small extents the abilities of the derivatives to inhibit microtubules assembly in vitro, result in significant difference in the order and the magnitude of the abilities of the drugs to inhibit cell growth.