Tannic acid attenuates the formation of cancer stem cells by inhibiting NF-kappa B-mediated phenotype transition of breast cancer cells

Abstract

Cancer stem cells (CSCs) are innately resistant to standard therapies, which positions CSCs in the focus of anti-cancer research. In this study, we investigated the potential inhibitory effect of tannic acid (TA) on CSCs. Our data demonstrated that TA (10 mu M), at the concentration not inhibiting the proliferation of normal mammary cells (MCF10A), inhibited the formation and growth of mammosphere in MCF7, T47D, MDA-MB-231 cells shown as a decrease in mammosphere formation efficiency (MFE), cell number, diameter of mammosphere, and ALDH1 activity. NF-kappa B pathway was activated in the mammosphere indicated by an up-regulation of p65, a degradation of IkBa, and an increased IL-6. The inhibition of NF-kappa B pathway via gene silencing of p65 (sip65), NF-kappa B inhibitor (PDTC), or I kappa K alpha, inhibitor (Bay11-7082) alleviated MFE. Other CSCs markers such as an increase in ALDH1 and CD44(high)/CD24(low) ratio were ameliorated by sip65. TA also alleviated TGF beta-induced EMT, increase in MFE, and NF-kappa B activation. In murine xenograft model, TA reduced tumor volume which was associated with a decrease in CD44(high)/CD24(low) expression and IKK phosphorylation. These results suggest that TA negatively regulates CSCs by inhibiting NF-kappa B activation and thereby prevents cancer cells from undergoing EMT and CSCs formation, and may thus be a promising therapy targeting CSCs.