Antimitotic Action of Griseofulvin does not Involve Disruption of Microtubules

Abstract

THE antimitotic action of griseofulvin in plant and mammalian cells has been attributed to a colchicine-like disruption of microtubules. Treatment of Vicia faba, Allium root tips or HeLa cells with griseofulvin, for example, resulted in the accumulation of cells at metaphase^1–3. The griseo-fulvin-inhibited cells contained abnormal arrays of chromosomes, identical to those produced by treatment of dividing cells with colchicine. Using polarization microscopy, Malawista et al.⁴ found that the addition of 10⁻⁵ M griseofulvin to dividing Pectinaria oocytes reduced the size of the nieiotic spindles, as measured by loss of birefringence. This action was considerably more rapid than with either podophyllotoxin or vinblastine sulphate; moreover, on removal of the griseofulvin, recovery of the spindle also occurred much more rapidly⁴. Recent evidence indicates that several of the drugs which arrest metaphase interfere with microtubule function through different mechanisms. Colchicine and the vinca alkaloids, for example, bind to tubulin (microtubule protein) at different molecular sites^5,6. Griseofulvin does not prevent the binding of colchicine to tubulin, nor does it affect the ability of the vinca alkaloids to stabilize the colchicine binding activity of tubulin⁵. This suggests that griseofulvin does not bind at either the colchicine or vinca alkaloid binding sites.