Epothilone D affects cell cycle and microtubular pattern in plant cells

Abstract

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.

Total Synthesis of Epothilone D: The Nerol/Macroaldolization Approach

“…NMR analysis confirmed the structure of compound 4 by comparison to the natural product and literature values of synthetic epothilone D (see the Supporting Information, page S52). Other spectroscopic and chromatographic properties, and eventually the antimitotic activity on human and plant cells, proved to be identical …”

Analysis of the Phialocephala subalpina Transcriptome during Colonization of Its Host Plant Picea abies

“…However, metabolic processes of macrolactones were found to be enriched at day 2. The macrocyclic lactone epothilone is known to have a phytotoxic effect on tomatoes [ 49 ] and from the transcriptome data of this study we assume it was biosynthesized by PAC two days after induction with Picea abies .…”