Natural estrogens induce modulation of microtubules in Chinese hamster V79 cells in culture.
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-beta-tubulin antibody. The effective concentrations of 17 beta-estradiol (E2-17 beta) and 17 alpha-estradiol required for the induction of microtubule distribution in 50% of the cells (EC50) in 1 h were 10 and 9 microM for V79 cells, respectively, and 2-methoxyestradiol showed the strongest activity (EC50 2 microM) 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 E2-17 beta, whereas 3-deoxy-3-methylestradiol showed almost the same EC50 value as E2-17 beta. There was a correlation between the EC50 values of the compounds and their growth-inhibitory activities. The presence of 1 microM taxol in culture protected against 50 microM E2-17 beta-induced microtubule disruption. Cycloheximide and actinomycin D had no preventive action on the effect of E2-17 beta, suggesting that the microtubule-disruptive effect of E2-17 beta is not associated with newly synthesized proteins and mRNAs. The present results indicate that some natural estrogens cause microtubule disruption in a nongenomic manner.
Aizu-Yokota
E
E
Division of Biochemistry, Kyoritsu College of Pharmacy, Tokyo, Japan.
Susaki
A
A
Sato
Y
Y
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D003513:Cycloheximide / Q000494:pharmacology; D003593:Cytoplasm / Q000648:ultrastructure; D003609:Dactinomycin / Q000494:pharmacology; D004958:Estradiol / Q000633:toxicity; D004967:Estrogens / Q000633:toxicity*; D008870:Microtubules / Q000187:drug effects*; D017239:Paclitaxel / Q000633:toxicity
D004967:Estrogens; D003609:Dactinomycin; D004958:Estradiol; D003513:Cycloheximide; D017239:Paclitaxel