Abstract P5-08-09: Tannic acid inhibited TGFβ-induced phenotype transition and mammosphere formation of breast cancer cells via modulation of NF-κB signaling
Authors: Kim D-A , Ryu E-S , Kang H-J , Kang D-H 
Published: May 2019

BACKGROUND: Cancer stem cells (CSCs) play a crucial role in tumor initiation, metastasis and recurrence, which are therefore regarded as promising therapeutic target. Aberrant NF-κB signaling has been identified in many cancers, and proven to promote CSC formation via several mechanisms, including an induction of epithelial-to-mesenchymal transition (EMT) of cancer cells. Tannic acid (C76H52O46, TA) was reported to inhibit the proliferation of cancer cells, however there was no data regarding the effect of TA on CSCs. The present study investigated the effects of TA on CSC formation, NF-κB signaling, and EMT in breast cancer cells.

MATERIALS AND METHODS: The effect of TA on mammosphere formation and the activity of aldehyde dehydrogenase 1 (ALDH1) was investigated in MCF7 cells. IKK phosphorylation, nuclear translocation of p65 and the expression of IκBα and CSCs markers (CD44/CD24, ALDH1) were assessed by western blotting. Role of NF-κB signaling in EMT of MCF7 cells were evaluated using p65 siRNA (sip65) and NF-κB specific inhibitor (PDTC) or IKK inhibitor (Bay11-7082). The effect of TA on tumor growth was also examined in a mouse xenograft model established by subcutaneous implantation of MCF7 cells (1.5 x 107) in 6-week-old Balb/c nude mice with intraperitoneal injection of TGFβ (40 ng/kg, 3 times/week). In 4 weeks of intraperitoneal administration of TA (2 mg/kg, twice/week), tumor volume was measured with an evaluation of the alteration of CSC markers and NF-κB signaling.

RESULTS: TA (10 μM) inhibited the formation and growth of mammosphere in MCF7 cells expressed as a decrease in mammosphere formation efficiency (MFE) and ALDH1 activity. An activation of NF-κB pathway was observed in MCF7-derived mammosphere shown as an up-regulation of p65, a degradation of IκBα and an increased IL-6. Blocking of NF-κB signaling by sip65, PDTC or Bay11-7082 resulted in a decrease in the MFE, the expression of ALDH1, and an increase in CD44high/CD24low ratio. TA alleviated the markers of NF-κB activation in MCF7-derived mammosphere. TGFβ (10 ng/mL)-induced EMT, increase in MFE and NF-κB activation was alleviated by TA. In murine xenograft model, tumor volume was decreased by TA with a decrease in CD44 expression and IKK phosphorylation in xenograft.

CONCLUSIONS: The present study showed that TA inhibited mammosphere formation in breast cancer cells, which was associated with an alleviation of both NF-kB signaling and EMT. Moreover, TA treatment ameliorated tumor growth in an in-vivo mouse xenograft of breast cancer. These data suggest TA may serve as an effective therapeutic agent for breast cancer patients.

Citation Format: Kim D-A, Ryu E-S, Kang H-J, Kang D-H. Tannic acid inhibited TGFβ-induced phenotype transition and mammosphere formation of breast cancer cells via modulation of NF-κB signaling [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-08-09.