Abstract 229: Pterostilbene suppresses the generation of breast cancer stem cells within tumor microenvironment and metastasis via modulating NF-κB/microRNA448 circuit.

Abstract

Abstract Tumor microenvironment plays a key role in promoting epithelial-to-mesenchymal transition (EMT), a cellular step for cancer cells to gain metastatic ability and is also associated to the generation of cancer stem cells (CSCs). Agents capable of modulating the tumor microenvironment could be more efficient in managing tumor progression. Pterostilbene, a natural stilbene isolated from blueberries have been suggested for its anti-cancer effects. Here, we explored the potential microenvironment modulating effects of pterostilbene in a M2-polarized macrophages (M2 TAMs) and breast cancer cell co-culture system. We first demonstrated that co-culturing with M2 TAMs increased the percentage of CD44+/CD24- CSC population and migratory/invasive abilities. We then showed that pterostilbene treatment dose-dependently overcame M2 TAM-induced enrichment of CSCs and metastatic potential of breast cancer cells. Mechanistically, pterostilbene suppressed NFκB, Twist1, Vimentin and increased E-cadherin expression. Importantly, pterostilbene-mediated NFκB downregulation was correlated to an increased amount of microRNA448. Finally, using non-invasive bioluminescence technique we demonstrated that pterostilbene treatment significantly suppressed M2 TAM co-cultured MDA-MB-231 tumorigenesis and metastasis. Thus, pterostilbene could be a potential anti-CSC agent for clinical development. Citation Format: Chi-Tai Yeh, Jeng-Fong Chiou, Chih-Hsiung Wu, Alexander TH Wu. Pterostilbene suppresses the generation of breast cancer stem cells within tumor microenvironment and metastasis via modulating NF-κB/microRNA448 circuit. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 229. doi:10.1158/1538-7445.AM2013-229