title: Proliferation, differentiation and apoptosis of choline deficient ethionine supplemented diet-rat oval cells under the influence of 2-methoxyestradiol.
abstract: Since numerous studies indicate that 2-methoxyestradiol (2-ME) as a metabolite of 17beta estradiol (17β-E(2)) may exert antitumor activity by unclear mechanism, we undertake the study to elucidate the effect of 2-ME on oval cells (OC) activated by a carcinogenic choline deficient ethionine supplemented diet (CDE diet). Isolated OC were treated with different concentrations of 2-ME for 24, 48 and 72 hours. In these periods of time phenotypic studies, apoptosis detection and proliferative activity of cells were performed. A marked inhibition of OC proliferation was observed at the presence of 1.0 μM of 2-ME, with the lowest value obtained after 48 h. However, at the end of the cells' incubation, maximally reduced proliferative response of OC was attributed to 2.0 μM of 2-ME. Simultaneously with the time of incubation the amount of Thy-1-positive cells decreased slightly from 50.5±1.4% to 31.5±3.6%. Contrary to 1.0 and 2.0 μM of 2-ME, its lowest value (0.5 μM) reduced Thy-1 positive cells after 48 hours. The same 2-ME concentration resulted in the elevation of the cell number expressing CK-19. In turn, the marked increase of albumine-positive cells was observed under 1.0 μM of 2-ME and reaching 21.5±6.2 % and 23.9±5.7% after 48 and 72 hours, respectively. Although the presence of 1.0 μM of 2-ME dramatically intensified apoptosis within 24 h of cell culture, the percentage of apoptotic cells remained unchanged under 2.0 μM of 2-ME. When subjected to the carcinogenic effect of CDE, 2-ME exerts anti-proliferative, proapoptotic, and differentiation effects in OC.
authors: Chair of Preclinical Veterinary Sciences, Department of Pathophysiology, Faculty of Veterinary Medicine, University of Life Sciences, Lublin, Poland. marta.wojcik@up.lublin.pl
authors: M
authors: M
authors: Wojcik
authors: R
authors: R
authors: Bobowiec
authors: U
authors: U
authors: Lisiecka
authors: K
authors: K
authors: Kostro
mesh_terms: D000077584:2-Methoxyestradiol; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D002796:Choline Deficiency / Q000378:metabolism / Q000473:pathology*; D004032:Diet; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005001:Ethionine / Q000008:administration & dosage*; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D015415:Biomarkers; D004958:Estradiol; D000077584:2-Methoxyestradiol; D005001:Ethionine