Oxaline, a fungal alkaloid, arrests the cell cycle in M phase by inhibition of tubulin polymerization.
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 [(3)H]colchicine to tubulin, but not that of [(3)H]vinblastine. These results indicate that oxaline inhibits tubulin polymerization, resulting in cell cycle arrest at the M phase.
Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University and The Kitasato Institute, 5-9-1 Shirokane, Minato, Tokyo 108-8641, Japan.
Yukio
Y
Koizumi
Masayoshi
M
Arai
Hiroshi
H
Tomoda
Satoshi
S
Omura
D000818:Animals; D001230:Aspergillus / Q000378:metabolism; D003078:Colchicine / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D051379:Mice; D008938:Mitosis / Q000187:drug effects*; D010407:Penicillium / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D014316:Tritium; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators; D014443:Tyrosine / Q000378:metabolism; D020687:cdc25 Phosphatases / Q000378:metabolism
C517976:Cdc25C phosphatase (211-221); D007093:Imidazoles; D010446:Peptide Fragments; D014404:Tubulin; D050257:Tubulin Modulators; C490207:oxaline; D014316:Tritium; D014443:Tyrosine; D006861:Hydrogen Peroxide; D020687:cdc25 Phosphatases; D003078:Colchicine