Correlates of Breast Cancer and Indole-3-Carbinol: Medicinal Development and Strategies of Natural Products

Estrogen-responsive breast cancer cells, such as MCF7 and T47D cells, express both estrogen receptor ER and ERß.Indole-3-carbinol (I3C) strongly down-regulated ER protein and transcript levels, without altering the level of ERßprotein, in both cell lines. In cells transfected with the ER promoter linked to a luciferase gene reporter, I3C ablatedER promoter activity1-5. Dietary indole-3-carbinol prevents the development of estrogen-enhanced cancers includingbreast. Whereas estrogen increases the growth and survival of tumors, indole-3-carbinol causes growth arrest andincreased apoptosis and ameliorates the effects of estrogen. In these findings best use indole-3-carbinol togetherwith other nutrients (genistein) to achieve maximum benefits for cancer prevention. Investigator evaluated whethergenistein, which is the major isoflavonoid in soy, would alter the ability of indole-3-carbinol/DIM to cause apoptosisand 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 andgenistein, the potential exists for prophylactic or therapeutic efficacy of lower concentrations of each phytochemicalwhen used in combination. I3C inhibits the enzyme elastase. High levels of elastase in breast cancer cells aresuggestive of a poor prognosis because elastase shortens cyclin E, a cellular chemical involved in controlling thecell cycle, and the shortened version of cyclin E speeds up the cell cycle, therefore making cancer cells proliferatefaster.I3C prevents the elastase shortening of cyclin E, thus halting the growth of breast cancer cells.