Epothilone D affects cell cycle and microtubular pattern in plant cells.
Epothilones, macrocyclic lactones from culture filtrates of the myxobacterium Sorangium cellulosum, are known as taxol-like microtubular drugs in human medicine. To date, nothing is known about the effect of epothilones on microtubules (MTs) in plant cells and/or on the plant cell cycle. As shown in this report, the treatment of tomato cell suspension cultures with epothilone D produced a continuous increase in the mitotic index. Dose-response curves revealed that epothilone D alters the mitotic index at concentrations as low as 1.5 microM. Mitotic arrest was already visible after only 2 h of treatment, and 55% of the cells were arrested after 24 h. As shown by immunocytological methods, abnormal spindles are formed during metaphase, which leads to a random distribution of chromosomes in the whole cell and prevents the formation of a metaphase plate. The process of chromosome decondensation does not seem to be affected, because micronuclei form at the same place with the distributed chromosomes. This suggests that epothilone D influences the stability of plant MTs mainly during metaphase of the mitotic cycle. In metaphase, the effects of epothilone D seem to be irreversible, because cells with an abnormal spindle could not be recovered after removal of the drug.
Hause
Gerd
G
Biozentrum der Universität, Martin-Luther-Universität Halle-Wittenberg, Weinbergweg 22, D-06120 Halle (Saale), Germany.
Lischewski
Sandra
S
Wessjohann
Ludger A
LA
Hause
Bettina
B
D002453:Cell Cycle / Q000187:drug effects*; D034261:Epothilones / Q000737:chemistry / Q000494:pharmacology*; D018551:Solanum lycopersicum / Q000166:cytology* / Q000187:drug effects*; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D015394:Molecular Structure; D017239:Paclitaxel / Q000494:pharmacology
D034261:Epothilones; D017239:Paclitaxel; C114026:desoxyepothilone B