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

• Published in: Applied biochemistry and microbiology Vol. 56; no. 9; pp. 909 - 919
• Main Authors: Poloznikov, A. A., Muyzhnek, E. L., Nikulin, S. V., Kaprin, A. D., Ashrafyan, L. A., Rozhkova, N. I., Labazanova, P. G., Kiselev, V. I.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01-12-2020
• Subjects: Biochemistry; Biologicals Technology; Biomedical and Life Sciences; Life Sciences; Medical Microbiology; Microbiology; breast cancer; indole-3-carbinol; Wnt; epigenetics
• ISSN: 0003-6838; 1608-3024
• DOI: 10.1134/S0003683820090070

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.