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

• Published in: Cell motility and the cytoskeleton Vol. 42; no. 1; p. 36
• Main Authors: Grellier, P, Sinou, V, Garreau-de Loubresse, N, Bylèn, E, Boulard, Y, Schrével, J
• Format: Journal Article
• Language: English
• Published: United States 1999
• Subjects: Animals; Blotting, Western; Cell Cycle - drug effects; Cell Division - drug effects; Cell Polarity; DNA, Kinetoplast - drug effects; DNA, Kinetoplast - ultrastructure; Dose-Response Relationship, Drug; Flagella - physiology; Fluorescent Antibody Technique; Giant Cells - ultrastructure; Microtubules - drug effects; Mitosis - drug effects; Mitosis - physiology; Morphogenesis; Time Factors; Trypanosoma cruzi - drug effects; Trypanosoma cruzi - metabolism; Trypanosoma cruzi - ultrastructure; Tubulin - immunology; Tubulin - metabolism; Vinca Alkaloids - pharmacology
• ISSN: 0886-1544; 1097-0169
• DOI: 10.1002/(SICI)1097-0169(1999)42:1<36::AID-CM4>3.0.CO;2-G

Vinca alkaloids, vincristine and vinblastine, produce differential effects on the cell division of Trypanosoma cruzi epimastigote forms depending on drug concentrations. These effects are related to different microtubule-based mechanisms. For 15 microM vinblastine and 50 microM vincristine, the drugs inhibit both nuclear division and cytokinesis, and affect cell shape. At 3 microM vinblastine and 10 microM vincristine, however, cytokinesis is inhibited without major effect on the progression of the cell cycle; this yields giant cells having multiple nuclei, kinetoplasts and flagella. Cultures maintained 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 inhibition by vinca alkaloids seems to result from modulations of interactions between microtubules and associated proteins, rather than from an inhibition of microtubule dynamics as is usually proposed for vinca alkaloids. Cytokinesis 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/kinetoplast complex. This region could play an essential role in cell morphogenesis since zoids (cells without a nucleus) are frequently observed.