Inhibition of estrogen-dependent breast cancer growth by a reaction product of alpha-fetoprotein and estradiol

Abstract

Reaction of picomolar quantities of human or rodent alpha-fetoprotein (AFP) with nanomolar quantities of 17 beta-estradiol (E2) generates a product of unknown structure, designated AFP/E2, that inhibits estrogen-stimulated growth of mouse uterus. We describe herein the effect of rodent AFP/E2 on the in vivo growth of two estrogen-dependent breast cancers, the MCF-7 human breast cancer and the MTW9A rat mammary cancer. Both cancers were grown as xenografts under the kidney capsule of cyclosporine-immunosuppressed male BDF1 mice. In addition, the MTW9A tumor was grown as a homograft in syngeneic ovariectomized Wistar-Furth female rats. Estrogen support was provided by s.c. Silastic E2 implants. Injecting AFP/E2 that was generated by incubating 1.0 microgram of AFP with 0.5 microgram of E2 for 1 h at room temperature resulted in cessation of growth and, in most cases, regression of MCF-7 tumor xenografts. It also produced regression of MTW9A tumor homografts and significantly inhibited growth of MTW9A xenografts. Treatment with AFP alone or E2 alone did not inhibit growth of these tumors. The data suggest that AFP/E2 has a unique property which causes attenuation or shut-down of the biochemical reactions through which estrogen-dependent tumor growth is mediated.