Genistein alone or combined with cyclophosphamide may stimulate 16/C transplantable mouse mammary cancer growth

Among the many potential antiangiogenic agents now in various stages of preclinical or clinical study, genistein (GEN) has generated wide interest being because of its natural origin (soybeans) and epidemiological studies showing the cancer chemopreventive effects of soybean consumption. In this paper the in vivo effects of GEN applied either alone or together with cyclophosphamide on the growth of mouse transplantable mammary carcinoma (16/C) transplanted either orthotopically or ectopically is presented. The growth of 16/C mouse mammary cancer transplanted subcutaneously (s.c.) or into the mammary gland (orthotopically-orth.) was stimulated by GEN administered from day 4 after tumor cell inoculation. Such stimulation was not observed when the treatment with GEN was started at day 12 after cell inoculation. Stimulation of tumor growth by GEN was markedly higher in mice transplantedorth. than in those transplanted s.c.. However, GEN did not affect the expression of estrogen (ER)and progesterone receptors (PgR) in the orthotopic model of 16/C cancer. In the case of subcutaneously growing tumors, treatment with GEN lowered (2-fold) the expression of both ER and PgR. In the interpretation of these results, the pleiotropic (including hormonal and antiproliferative), sometimes opposing effects of genistein in vivo should be considered. It seems rather reasonable to exclude breast and, perhaps, other hormone-dependent cancers from the treatment and chemoprevention with soy-derived phytoestrogens until its mechanism(s) of action on various cancer cells is completely understood.