Effect of the microtubule stabilising agent taxol on leishmanial protozoan parasites in vitro.
Taxol, a mitotic spindle toxin, was found to selectively inhibit the proliferation of Leishmania donovani in vitro at nanomolar concentrations with an IC50 of 35 nM. Concentrations of taxol as high as 50 nM, however, did not affect J774A.1 murine macrophages. Taxol (30 nM) also inhibited amastigote multiplication within a J774A.1 macrophage cell line when used in a 10-day experiment. It resulted in the in vitro assembly of L. donovani microtubules in a dose-dependent manner. When promastigotes were exposed to different concentrations of taxol for 24 h, cells were largely blocked in the G2-M phase of the cell cycle and there was a marked reduction in the percentage of cells in the S phase. The selective nature of taxol action against the parasite and its effectiveness in controlling amastigote multiplication emphasise its use as a promising chemotherapeutic against kala-azar.
Kapoor
P
P
School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
Sachdeva
M
M
Madhubala
R
R
D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D007893:Leishmania donovani / Q000187:drug effects* / Q000254:growth & development; D008870:Microtubules / Q000187:drug effects*; D017239:Paclitaxel / Q000494:pharmacology*; D014404:Tubulin / Q000187:drug effects
D000981:Antiprotozoal Agents; D014404:Tubulin; D017239:Paclitaxel