Breast Cancer and Indole -3-Carbinol: Controversy of Estrogen Level and Enzyme Elastase

Estrogen-responsive breast cancer cells, such as MCF7 and T47D cells, express both estrogen receptor ERα and ERß. Indole-3-carbinol (I3C) strongly down-regulated ERα protein and transcript levels, without altering the level of ERß protein, in both cell lines. In cells transfected with the ERα promoter linked to a luciferase gene reporter, I3C ablated ERα promoter activity^1–5. Dietary indole-3-carbinol prevents the development of estrogen-enhanced cancers including breast. Whereas estrogen increases the growth and survival of tumors, indole-3-carbinol causes growth arrest and increased apoptosis and ameliorates the effects of estrogen. Our goal is to best use indole-3-carbinol together with other nutrients (genistein) to achieve maximum benefits for cancer prevention. We evaluated whether genistein, which is the major isoflavonoid in soy, would alter the ability of indole-3-carbinol/DIM to cause apoptosis and decrease expression driven by the estrogen receptor (ER)-alpha. Synergistic effect of indole-3-carbinol and genistein for induction of GADD expression, thus increasing apoptosis, and for decrease of expression driven by ER-alpha. Because of the synergistic effect of indole-3-carbinol and genistein, the potential exists for prophylactic or therapeutic efficacy of lower concentrations of each phytochemical when used in combination.¹¹ I3C inhibits the enzyme elastase. High levels of elastase in breast cancer cells are suggestive of a poor prognosis because elastase shortens cyclin E, a cellular chemical involved in controlling the cell cycle, and the shortened version of cyclin E speeds up the cell cycle, therefore making cancer cells proliferate faster.I3C prevents the elastase shortening of cyclin E, thus halting the growth of breast cancer cells.