Natural estrogens and their derivatives comprising 30 compounds in total were tested for their ability to induce microtubule disruption in Chinese hamster V79 cells. The cytoplasmic microtubule networks were examined by the indirect immunofluorescence method using anti-β-tubu-lin antibody. The effective concentrations of 17β-estradfol (Ej-Hβ) and 17α-estradiol required for the induction of microtubule distribution in 50% of the cells (EC50) in 1 h were 10 and 9 µm for V79 cells, respectively, and 2-methoxyestradiol showed the strongest activity (ECso 2 µm) among the tested compounds including the catechol estrogens 2-hydroxyestradiol, 4-hydroxyestradiol, 2-hydroxyestrone, and 4-hydroxyestrone. The estrone series of estrogens showed relatively low activity for disruption of microtubule networks compared with E2-17β, whereas 3-deoxy-3-methylestra-diol showed almost the same EC50 value as E2-17β. There was a correlation between the EC50 values of the compounds and their growth-inhibitory activities. The presence of 1 µm taxol in culture protected against 50 µm E2-17β-induced microtubule disruption. Cydoheximide and actinomydn D had no preventive action on the effect of E2-17β, suggesting that the microtubule-disruptive effect of E2-17β is not associated with newly synthesized proteins and mRNAs. The present results indicate that some natural estrogens cause microtubule disruption in a nongenomk manner.
|出版ステータス||Published - 1995 5月 1|
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