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Inhibition of Angiogenesis by Antiestrogens¹

Research Service, Veterans Affairs Medical Center [A. G., D. C. C.], and Departments of Physiology [A. G.] and Obstetrics and Gynecology [D. C. C.], University of Kentucky College of Medicine, Lexington, Kentucky 40536

In this study, we have determined the ability of the partial estrogen antagonists, clomiphene, tamoxifen, and nafoxidine, and the pure estrogen antagonists, ICI 164,384 and ICI 182,780, to inhibit angiogenesis in the chick egg chorioallantoic membrane. All of the partial estrogen antagonists and the pure estrogen antagonist, ICI 182,780, showed significant angiostatic activity in a dose-related manner. The addition of up to 5-fold of 17ß-estradiol to the disks containing clomiphene, tamoxifen, or ICI 182,780 did not alter the angiostatic activity of these antiestrogens.

These novel findings show that the antiestrogens are effective inhibitors of angiogenesis. The finding that angiostatic activity is not altered in the presence of excess estrogens suggests that this activity is exerted via mechanisms other than their inhibition of estrogen action. This angiostatic activity may contribute to the therapeutic effect of antiestrogens in estrogen receptor-negative tumors.

¹ This work was supported by NIH Grant R01-HL43035 and the Department of Veterans Affairs. Dr. Antonio Gagliardi is sponsored by CAPES (Brazil), PROC:901/90-3.

² To whom requests for reprints should be addressed, at A-301 Kentucky Clinic, University of Kentucky Medical Center, Lexington, KY 40536-0284.

Received 9/10/92. Accepted 11/19/92.

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