Analysis of Tumor‑Suppressive Effects of Soy Isoflavones on Estrogen‑Independent Mammary Carcinoma Cells

In vivo and in vitro studies have indicated that the isoflavones including genistein in soybeans may be responsible for mammary tumor suppressive effects. We confirmed the tumor suppressive effects of soy isoflavones using c-Ha-ras transgenic rats which develop estrogen-independent as well as estrogen-dependent mammary carcinomas. Three estrogen receptor positive, cell lines C3, C11 and C17 (estrogen receptor β positive) among seven lines established from the tumors in this transgenic rat were tested for estrogen responsiveness and revealed as estrogen-independent cells. Genistein at ≧50μM of concentration suppressed DNA synthesis of these rat cell lines as well as MCF-7 human cells even in the presence of estrogen. In contrast, the inhibitory effect of genistein was only observed on estrogen-independent C3 and C11 cells in the absence of estrogen. Cell cycle was arrested at G2/M phase and apoptosis was induced in C11 cells after 72 hr incubation with 10μM genistein. A number of genes encoding transcription factors and apoptosis-related factors were included in the genes that showed >2-fold change in their expression levels after the treatment of C11 cells. These results suggest that genistein suppresses mammary carcinomas mainly due to cell cycle arrest at G2/M phase and an apoptosis-inducing effect in an estrogen receptor-independent manner. Soy Protein Research, Japan 8, 127-132, 2005.