The cytotoxic effects of estradiol-17 beta, catecholestradiols and methoxyestradiols on dividing MCF-7 and HeLa cells
| Autor: | J.C. Seegers, Casper H. van Aswegen, Mona-Liza Aveling, Willem S. Joubert, Marissa Cross, Francois Koch |
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| Rok vydání: | 1989 |
| Předmět: |
Metabolite
Fluorescence spectrometry Biology Hydroxylation Biochemistry HeLa chemistry.chemical_compound Endocrinology Tubulin Mitotic Index Cytotoxic T cell Humans Metaphase Benzoflavones Quinalizarin Estradiol biology.organism_classification Molecular biology Immunohistochemistry Estrogens Catechol chemistry Cell culture Multipolar spindles Cell Division HeLa Cells |
| Zdroj: | Journal of steroid biochemistry. 32(6) |
| ISSN: | 0022-4731 |
| Popis: | In this study the cytotoxic effects of high concentrations (greater than or equal to 1 x 10(-6) M) of estradiol-17 beta (E2), 2-/4-hydroxyestradiol-17 beta (2-/4-OHE2) and 2-/3-/4-methoxyestradiol-17 beta (2-/3-/4-MeOE2) were determined on dividing MCF-7 and HeLa cells. The 2-MeOE2 metabolite followed by 2-OHE2 and E2 (in this order) proved to be extremely toxic to dividing MCF-7 and HeLa cells. The cytotoxic effect on these cells comprised uneven chromosome distribution. Indirect immunofluorescent studies, in which monoclonal anti-alpha-tubulin antibodies were used, showed that these compounds (2-MeOE2 greater than 2-OHE2 greater than E2) at high concentrations caused abnormal and fragmented polar formations as well as disorientated microtubule arrangement in the dividing MCF-7 and HeLa cells. The 4-OHE2 and 3-/4-MeOE2 metabolites had little or no cytotoxic effects on dividing cells. The large number of abnormal metaphases seen in HeLa cells exposed to 2-MeOE2 suggested that this metabolite may be the ultimate cytotoxic compound. The reduction in the number of HeLa cells with abnormal metaphase configurations after exposure to 2-OHE2 plus quinalizarin (an inhibitor of catechol-O-methyltransferase) indicated that the production of 2-MeOE2 is necessary for the formation of abnormal spindles in metaphase. Quinalizarin treatment in the presence of 2-MeOE2 had no effect on the large number of abnormal metaphases. We therefore conclude that neither E2 nor 2-OHE2, but a high concentration of 2-MeOE2 is responsible for abnormal spindle formation. In additional experiments the number of normal and abnormal dividing HeLa cells were greatly reduced when simultaneously exposed to E2 and 2-/4-hydroxylase-inhibitor alpha-naphthoflavone. |
| Databáze: | OpenAIRE |
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