期刊
REPRODUCTIVE SCIENCES
卷 21, 期 1, 页码 102-111出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/1933719113492211
关键词
E-2 beta; E-2 beta metabolites; ascorbic acid; ovarian cancer cells; growth
资金
- National Institutes of Health [HD38843, HL49210, HL87144]
Estradiol 17 beta (E-2 beta) and ascorbic acid (AA) have been implicated in cancer progression. However, little is known about the actions of biologically active metabolites of E-2, 2-hydroxyestradiol (2OHE(2)), 4-hydroxyestradiol (4OHE(2)), 2-methoxyestradiol (2ME(2)), and 4-methoxyestradiol (4ME(2)) synthesized sequentially by cytochrome P450, family 1, subfamily A (CYP1A1) and B (CYP1B1), polypeptide 1, and catechol-O-methyltransferase (COMT) on ovarian cancer. Herein, we examined the expression of CYP1A1, CYP1B1, COMT, and estrogen receptor (ER) and (ER) in human ovarian surface epithelial (IOSE-385) and cancer cell lines (OVCAR-3, SKOV-3, and OVCA-432). We also investigated the roles of E-2, 2OHE(2), 4OHE(2), 2ME(2), and 4ME(2) in cell proliferation, and their interactive effects with AA on ovarian cells. We found the expression of CYP1A1, CYP1B1, COMT, ER, and ER in most cell lines tested. Treating cells with physiological concentrations of E-2 and its metabolites promoted (13%-42% of the control) IOSE-385 and OVCAR-3 proliferation. The ER blockade inhibited IOSE-385 (approximate to 76%) and OVCAR-3 (approximate to 87%) proliferative response to E-2 but not to its metabolites. The ER blockade inhibited (approximate to 85%) E-2-stimulated OVCAR-3 proliferation, whereas ER blockade attenuated (approximate to 83%) E-2-stimulated IOSE-385 proliferation. The AA at 250 mol/L completely inhibited serum-stimulated cell proliferation in all cell lines tested; however, such inhibition in IOSE-385, OVCAR-3, and OVCA-432 was partially (approximate to 10%-20%) countered by E-2 and its metabolites. Thus, our findings indicate that E-2 and its metabolites promote cell proliferation and antagonize the AA-suppressed cell proliferation in a subset of ovarian cancer cells, suggesting that blocking the actions of E-2 and its metabolites may enhance AA's antiovarian cancer activity.
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