Ellagitannins, promising pharmacological agents for the treatment of cancer stem cells.

Human tumors comprise subpopulations of cells called cancer stem cells (CSCs) that possess stemness properties. CSCs can initiate tumors and cause recurrence, metastasis and are also responsible for chemo- and radio-resistance. CSCs may use signaling pathways similar to normal stem cells, including Notch, JAK/STAT, Wnt and Hedgehog pathways. Ellagitannins (ETs) are a broad group of substances with chemopreventive and anticancer activities. The antitumor activity of ETs and their derivatives are mainly related to their antiinflammatory capacity. They are therefore able to modulate secretory growth factors and pro-inflammatory mediators such as IL-6, TGF-β, TNF-α, IL-1β and IFN-γ. Evidence suggests that ETs display their anticancer effect by targeting CSCs and disrupting stem cell signaling. However, there are still few studies in this field. Therefore, high-quality studies are needed to firmly establish the clinical efficacy of the ETs on CSCs. This paper reviews the structures, sources and pharmacokinetics of ETs. It also focuses on the function of ETs and their effects on CSCs-related cytokines and the relationship between ETs and signaling pathways in CSCs.