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An estrogen metabolite, 2‐methoxyestradiol, promotes coronary artery dilation and inhibits breast cancer proliferation
Author(s) -
Hill Brent J.F.,
Schlicker Bonnie,
Jordan Renee,
Runge Steven W.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.1032.4
Subject(s) - 2 methoxyestradiol , metabolite , estrogen , medicine , endocrinology , incubation , breast cancer , contraction (grammar) , apoptosis , chemistry , pharmacology , cancer , biochemistry
The cardioprotective benefit of estrogen (E2) has been well documented; however, its use in hormone replacement therapy has accentuated the development of breast cancer in some women. The purpose of this study was to compare the E2 metabolite, 2‐methoxyestradiol (2‐MeOH), with E2 on coronary arterial tone. Coronary arteries were dissected out of hearts obtained from female pigs, sectioned into 4 mm rings, and suspended in organ baths. A 60‐minute pre‐incubation using 10 [micro]M E2 and 2‐MeOH similarly inhibited a KCl and endothelin‐1‐induced contraction by 50% and 36%, respectively; thus, demonstrating inhibition of Ca 2+ influx. Also, the K + channel blocker, TEA (1 mM), enhanced the KCl‐induced contraction by 20 % after the pre‐incubation with 1 [micro]M 2‐MeOH, but not 10 [micro]M 2‐MeOH, this suggests 2‐MeOH stimulates Ca 2+ ‐activated K + channels. Breast cancer (MCF‐7) cells were incubated over a 6 day period with 1 nM E2 and 2‐MeOH in a normoxic and hypoxic environment. In contrast to E2, cell counts indicated that 2‐MeOH decreased the cell number by 39% and 32% in normoxic and hypoxic conditions, respectively. Overall, our data suggest that 2‐MeOH may be a therapeutic alternative in hormone replacement therapy because of its apoptotic effect on breast cancer and its similarity to the E2 cardioprotective effect on coronary tone. Support: NCRR of the NIH, Grant #P20 RR‐16460