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, 17β-estradiol (E2) prevents tumor formation in ovariectomized females. We examined human CRC intestinal cell lines to determine whether particular E2 metabolites produced anti-tumor effects. Treatment of CRC cells with 2-methoxyestradiol (2-MeOE2) increased expression of p53 and p21WAF1/CIP1 proteins and induced apoptosis, but did not produce changes in expression of estrogen receptor (ER)α or ERβ. The finding that 2-MeOE2 induces p53-mediated colon cell apoptosis in vitro supports a role for 2-MeOE2 as an endogenous mediator of intestinal tumor suppression.