Selective and reversible effects of vinca alkaloids on Trypanosoma cruzi epimastigote forms: Blockage of cytokinesis without inhibition of the organelle duplication

Citation
P. Grellier et al., Selective and reversible effects of vinca alkaloids on Trypanosoma cruzi epimastigote forms: Blockage of cytokinesis without inhibition of the organelle duplication, CELL MOTIL, 42(1), 1999, pp. 36-47
Citations number
43
Categorie Soggetti
Cell & Developmental Biology
Journal title
CELL MOTILITY AND THE CYTOSKELETON
ISSN journal
08861544 → ACNP
Volume
42
Issue
1
Year of publication
1999
Pages
36 - 47
Database
ISI
SICI code
0886-1544(1999)42:1<36:SAREOV>2.0.ZU;2-6
Abstract
Vinca alkaloids, vincristine and vinblastine, produce differential effects on the cell division of Trypanosoma cruzi epimastigote forms depending on d rug concentrations. These effects are related to different microtubule-base d mechanisms. For 15 mu M vinblastine and 50 mu M vincristine, the drugs in hibit both nuclear division and cytokinesis, and affect cell shape. At 3 mu M vinblastine and 10 mu M vincristine, however, cytokinesis is inhibited w ithout major effect on the progression of the cell cycle; this yields giant cells having multiple nuclei, kinetoplasts and flagella. Cultures maintain ed over 1 week with daily drug replacement produced cells with more than 16 nuclei and 24 kinetoplasts. indicating that an equivalent of a fifth cell cycle was initiated. The ultrastructure of the multinucleate cells showed a basic organization closely similar to that of trypanosomes. Cytokinesis in hibition by vinca alkaloids seems to result from modulations of interaction s between microtubules and associated proteins, rather than fi om an inhibi tion of microtubule dynamics as is usually proposed for vinca alkaloids. Cy tokinesis inhibition is reversible: after removing the drug, epimastigotes emerge from the multinucleate cells. The emerging process follows a precise axis and polarity which are determined by the position of the flagellum/ki netoplast complex. This region could play an essential role in cell morphog enesis since zoids (cells without a nucleus) are frequently observed. Cell Motil. Cytoskeleton 42:36-47, 1999, (C) 1999 Wiley-Liss, Inc.