Control of Breast Tumor Cell Growth by Dietary Indoles
Final rept. 1 Sep 1996-31 Aug 2000
CALIFORNIA UNIV BERKELEY
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Indole-3-carbinol 13 C is a naturally occurring component of dietary vegetables and a promising preventive agent against breast cancer. To further examine the properties of 13C and to establish the mechanism of action of this novel antiestrogen, we pursued the following specific aims a Identify 13C products that are responsible for 13Cs growth inhibitory effects in breast tumor cells. b Characterize effects of indoles on estrogen receptor- and Ah receptor-mediated cellular responses. c Identify genes involved in the indole-mediated inhibition of growth of mammary tumor cells. In summary, and contrary to our expectations, we found that high concentrations of 13C strongly and reversibly inhibited proliferation of cultured breast tumor cells accompanied by a specific arrest in the cell cycle. In contrast, however, the primary in vitro effects of the major in vivo products of I3C, i.e. DIM and CTr-1, were to activate estrogen receptor function and to promote proliferation of estrogen-dependent cells. Our results of gene expression analyses showed that the effects of DIM treatment on breast tumor cells were most pronounced in a group of genes important in late stage tumor growth and metastasis. Taken together, these results reveal distinct and promising cancer protective or chemotherapeutic activities of 13C and its in vivo products.
- Anatomy and Physiology
- Medicine and Medical Research