Suppression of breast cancer invasion and migration by indole-3-carbinol: associated with up-regulation of BRCA1 and E-cadherin/catenin complexes

Abstract

Indole-3-carbinol (I3C) is a compound occurring naturally in cruciferous vegetables and has been indicated as a promising agent in preventing breast cancer development and progression. In the present study we have investigated the effect of I3C on the cell migration and invasion behavior in estrogen receptor positive MCF-7 and estrogen receptor negative MDA-MB-468 human breast cancer cell lines. Both MCF-7 and MDA-MB-468 were poorly invasive cell lines and exhibited modest invasion and migration capacity in the presence of fibronectin as the chemoattractant. I3C (50 or 100 µM) elicited a significant inhibition of in vitro cell adhesion, migration, and invasion as well as in vivo lung metastasis formation in both cell lines. I3C also suppressed the 17β-estradiol stimulated migration and invasion in estrogen-responsive MCF-7 cells. These results indicate that anti-invasion and antimigration activities of I3C occur via estrogen-independent and estrogen-dependent pathways. Moreover, I3C significantly caused a dose-dependent increase in E-cadherin, three major catenins (α, β, and γ-catenin) and BRCA1 expression. Our current finding is the first demonstration that I3C can activate the function of invasion suppressor molecules associated with the suppression of invasion and migration in breast cancer cells. Thus, clinical application of I3C may contribute to the potential benefit for suppression of breast cancer invasion and metastasis.