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 with 100 ng/ml bistratene A was found to inhibit cytokinesis but had no effect on DNA synthesis and nuclear division. Consequently, bistratene A-treated cells became polyploid and multinucleate. In association with the development of this phenotype, the cytoplasmic protein stathmin was biphasically phosphorylated and levels of expression were doubled. Immunostaining of binucleate cells (bistratene A for 24 h) revealed increased alpha-tubulin localization where the cleavage furrow might be expected to form, i.e., along the equatorial plane. Treatment of these binucleate cells with the microtubule depolymerizing agent nocadazole promoted cleavage furrow formation and partially ameliorated the bistratene A-induced block in cell division. These findings implicate the polymerization status of microtubules and stathmin function in the regulation of cytokinesis.
Johnson
W E
WE
Centre for Spinal Studies, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, Shropshire, SY10 7AG, United Kingdom. w.e.b.johnson@keele.ac.uk
Watters
D J
DJ
Suniara
R K
RK
Brown
G
G
Bunce
C M
CM
D000081:Acetamides; D000970:Antineoplastic Agents / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004988:Ethers, Cyclic / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D008868:Microtubule Proteins; D008870:Microtubules / Q000187:drug effects*; D015739:Nocodazole / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism*; D011714:Pyrans; D013141:Spiro Compounds; D050777:Stathmin; D013997:Time Factors; D014404:Tubulin / Q000032:analysis
D000081:Acetamides; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D004988:Ethers, Cyclic; D006131:Growth Inhibitors; D008868:Microtubule Proteins; D010750:Phosphoproteins; D011714:Pyrans; C493995:STMN1 protein, human; D013141:Spiro Compounds; D050777:Stathmin; D014404:Tubulin; C059975:bistratene A; D017239:Paclitaxel; D015739:Nocodazole