Abstract
Abstract Cancer stem cells (CSCs) have been defined as a subpopulation of cancer cells with the ability of self-renewal, giving rise to different progenies, and transition between epithelial and mesenchymal status in response to the tumor microenvironment. Due to the lack of an appropriate cell model, our understanding of CSC biology remains poor and the development of CSC antagonists is challenging. We herein used the UP-LN1 cell line as a CSC model which was derived from a gastrointestinal tumor-to-lymph node metastasis lesion. UP-LN1 cells constitute two major components, the floating (F) and adherent (A) cells. F cells were identified as the primary niche of CSCs, and could be serially subcultured while maintaining their stem-like properties including high self-renewal potential, formation of suspended grape-like aggregates and/or spheres, resistance to multiple drugs and NK/LAK effectors, as well as an increased CDY1 (a novel iPS probe) dye retention. Using this cell model, we demonstrated that Withaferin A (WA) dramatically reduced the proliferation of F cells and their ability to form aggregates in vitro. WA also dose-dependently reduced the side population cells. Mechanistically, WA treatment resulted in the down-regulation of two axes, CXCR4 and STAT3, both instrumental in the acquisition of metastatic ability and the development/maintenance of CSCs. We validated the in vitro results using non-invasive imaging technique in a xenograft mouse model. WA-treated animals demonstrated a marked decrease in tumor burden and metastasis, indicating that WA is potentially an effective agent for targeting CSCs. Citation Format: Chi-Tai Yeh, Alexander TH Wu, Hung-Chang Chen, Cheng-Keng Chuang, See-Tong Pang, Shuen-Kuei Liao. Anticancer effects of Withaferin A on UP-LN1 carcinoma cells through the inhibition of STAT3 phosphorylation and IFN-γ-mediated induction of metastatic cancer stem cells . [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 222. doi:10.1158/1538-7445.AM2013-222
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