Sinefungin and Taxol Effects on Cell Cycle and Cytoskeleton ofLeishmania donovaniPromastigotes

• DOI: 10.1006/excr.1996.0229
• Publication Date: 2002-10-07T11:40:37Z
• Authors: Lamya Moulay; Malka Robert-Gero; Spencer Brown; Marie-Claude Gendron; Frédéric Tournier
• Keywords: 0301 basic medicine; Adenosine; Paclitaxel; Cell Cycle; Antiprotozoal Agents; Plicamycin; DNA, Protozoan; Flow Cytometry; Microtubules; Actins; 03 medical and health sciences; Animals; Cytoskeleton; Fluorescent Dyes; Leishmania donovani

Sinefungin is an antibiotic possessing a strong anti-leishmanial activity. Among the most important effects of this molecule on Leishmania donovani promastigotes are morphological modifications and a very rapid and effective inhibition of DNA synthesis. These cells contain a single DNA-rich mitochondrion whose division cycle is coordinated with the nuclear division cycle. We have developed a flow-cytometric procedure based upon mithramycin as fluorochrome that can perform quantitative cell cycle analysis on the nuclear DNA. Cell cycle progression was analyzed to establish that sinefungin irreversibly blocks the promastigotes in early S phase. Sinefungin did not react with stationary cells as they were arrested in G1. Surprisingly, taxol, a microtubule-stabilizing drug, induced the same morphological modifications as sinefungin although it interfered with the G2/M progression. According to immunofluorescence studies, the stable microtubular network is apparently affected neither by taxol nor by sinefungin.