2-Methoxyestradiol induces p53-associated apoptosis of colorectal cancer cells.
Menopausal estrogen replacement therapy is thought to be responsible for the recent decline in colorectal cancer (CRC) incidence among women. In the C57BL/6J-Min/+ mouse, an animal model of CRC, 17beta-estradiol (E(2)) prevents tumor formation in ovariectomized females. We examined human CRC intestinal cell lines to determine whether particular E(2) metabolites produced anti-tumor effects. Treatment of CRC cells with 2-methoxyestradiol (2-MeOE(2)) increased expression of p53 and p21(WAF1/CIP1) proteins and induced apoptosis, but did not produce changes in expression of estrogen receptor (ER)alpha or ERbeta. The finding that 2-MeOE(2) induces p53-mediated colon cell apoptosis in vitro supports a role for 2-MeOE(2) as an endogenous mediator of intestinal tumor suppression.
D000077584:2-Methoxyestradiol; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D006801:Humans; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011960:Receptors, Estrogen; D016159:Tumor Suppressor Protein p53; D004958:Estradiol; D000077584:2-Methoxyestradiol; D011065:Poly(ADP-ribose) Polymerases