Proliferation,differentiation and apoptosis of choline deficient ethionine supplemented diet-rat oval cells under the influence of 2-methoxyestradiol

Since numerous studies indicate that 2-methoxyestradiol (2-me) as a metabolite of 17beta estradiol (17β-e2) 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. amarked 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.