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