Identification of the concentration dependent effects of estrogen in human endometrial cancer cells.

Estrogen is known to stimulate growth and development of endometrial cells in uterus in humans. In order to characterize the effect of estrogen on endometrial cells we used the differentiated human endometrial cancer derived Ishikawa cell line. We first evaluated the effect of 17-ß-estradiol (estradiol) on cell viability as determined by trypan blue exclusion assay. Interestingly, at concentrations above physiological levels of estrogen in serum, estradiol (1-25 ?M) induced a concentration-dependent cell death in Ishikawa cells under low serum conditions. We found that similar concentrations of estradiol inhibited cell growth as shown by immunocytochemical staining of proliferating cell nuclear antigen (PCNA) expression and 5-bromo-2'-deoxyuridine (BrdU) incorporation assays. We further determined by Terminal deoxynucleotidyl transferase (TdT) -mediated dUTP nick end labelling (TUNEL) analysis that the cell death induced by estradiol showed the characteristics of apoptosis, such as shrinkage of cytoplasm, chromatin condensation and DNA fragmentation.Our data showing the apoptotic effect of high concentrations of estradiol in low serum conditions, which mimic the low estrogenic environment in menopause, suggest that high doses of estrogen can induce regression of hormone-dependent endometrial cancer in postmenopausal women.