Antitumor Activity of Indole-3-carbinol in Breast Cancer Cells: Phenotype, Genetic Pattern, DNA Methylation Inversion

The effect of indole-3-carbinol on the proliferation and migration of MDA-MB-231 breast-cancer cells and healthy MCF-10A breast-tissue cells has been studied. It was shown that indole-3-carbinol reliably reduced the proliferation and migration of MDA-MB-231 cells and does not significantly affect MCF-10A cells. The incubation of MDA-MB-231 tumor cells with 100 μM indole-3-carbinol for 48 h resulted in a marked decrease in the expression of the Wnt cascade genes CCND1 (by 28%), Sp1 (by 44%), CDK6 (by 47%), as well as the EGFR and FASN genes (by 64 and 22%, respectively). Incubation of the MCF-10A cell line under the same conditions induced a noticeable decrease in the expression of only two genes, EGFR (by 16%) and CDK6 (by 9%). Indole-3-carbinol was also shown to display selective DNA demethylating activity in breast-tumor cells and to reverse the process of abnormal methylation and functional blockage of the antitumor WIF-1 gene. The obtained data indicate that drugs containing indole-3-carbinol as an active component can be potential regulators of epigenetic processes in the complex treatment of breast cancer and other tumors.