Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
Volume 1693, Issue 1, Pages 47-55Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamcr.2004.04.013
Keywords
fungal alkaloid; oxaline; cell cycle; microtubule; tubulin
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Oxaline and neoxaline, fungal alkaloids, were found to inhibit cell proliferation and to induce cell cycle arrest at the G(2)/M phase in Jurkat cells. CBP501 (a peptide corresponding to amino acids 211-221 of Cdc25C phosphatase), which inhibits the G(2) checkpoint, did not affect the G(2)/M arrest caused by oxaline, suggesting that oxaline causes M phase arrest but not G(2) phase arrest. The Cdc2 phosphorylation level of oxaline-treated cell lysate was lower than that of the control cells, indicating that oxaline arrests the M phase. Oxaline disrupted cytoplasmic microtubule assembly in 3T3 cells. Furthermore, oxaline inhibited polymerization of microtubule protein and purified tubulin dose-dependently in vitro. In a binding competition assay, oxaline inhibited the binding of [H-3]colchicine to tubulin, but not that of [H-3]vinblastine. These results indicate that oxaline inhibits tubulin polymerization, resulting in cell cycle arrest at the M phase. (C) 2004 Elsevier B.V. All rights reserved.
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