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LOVASTATIN INDUCES MITOTIC ABNORMALITIES IN VARIOUS CELL LINES

1999; Wiley; Volume: 23; Issue: 1 Linguagem: Inglês

10.1006/cbir.1998.0322

1095-8355

J Lamprecht, Cezary Wójcik, Marek Jakóbisiak, Micheal Stoehr, Dieter Schrorter, Neidhard Paweletz,

Protein Structure and Dynamics

We examined the effects of lovastatin, a common anti‐atherosclerotic drug and a blocker of the cell cycle, on the process of mitosis. It is known that lovastatin induces an arrest or a retardation of the cell cycle in many cell types not only at the G 1 phase, but also at the G 2 /M transition. After 24–48h incubation of epithelial PtK 2 , T24, HeLa cells and fibroblastic L929 cells in the presence of 1.0–60.0μm lovastatin, diverse mitotic perturbations have been observed. The most noteworthy phenomena recorded were prometaphase retardation and chromosome lagging during metaphase and anaphase. After the recovery in lovastatin‐free media, the cells continued mitosis without any disturbances. Mevalonic acid prevented the effects of lovastatin. We conclude that the effects were specific for lovastatin‐induced inhibition of mevalonic acid synthesis. Immunofluorescence studies with anticentromeric antibodies suggested that one of the possible causes of the lovastatin‐induced mitotic disorder could be an interference with the development and function of the centromeres.