Bistratene A induces a microtubule-dependent block in cytokinesis and altered stathmin expression in HL60 cells

Bistratene A is a cyclic polyether which affects cell cycle progression and can induce phosphorylation of cellular proteins. Treatment of HL60 cells w ith 100 ng/ml bistratene A was found to inhibit cytokinesis but had no effe ct on DNA synthesis and nuclear division. Consequently, bistratene A-treate d cells became polyploid and multinucleate. In association with the develop ment of this phenotype, the cytoplasmic protein stathmin was biphasically p hosphorylated and levels of expression were doubled. Immunostaining of binu cleate cells (bistratene A for 24 h) revealed increased alpha-tubulin local ization where the cleavage furrow might be expected to form, i.e., along th e equatorial plane. Treatment of these binucleate cells with the microtubul e depolymerizing agent nocadazole promoted cleavage furrow formation and pa rtially ameliorated the bistratene A-induced block in cell division. These findings implicate the polymerization status of microtubules and stathmin f unction in the regulation of cytokinesis. (C) 1999 Academic Press.