Curcumin Effects on the Wnt Signaling Pathway in Colorectal Cancer Stem Cells

Colorectal cancer (CRC) is a leading cause of death worldwide. Despite improved treatment procedures, the disease can rarely be cured completely mainly due to its recurrence. It has been proved that cancer recurrence is caused by cancer stem cells (CSCs); rare and immortal cells which have the ability to initiate and develop tumors and protect them against anticancer agents. CSCs are generated as a result of failures in intracellular signaling pathways, in which Wnt/β-catenin plays a major role in colorectal cancer. The Wnt/β-catenin signaling pathway is thought to be the major pathway in the maintenance of homeostasis of intestinal stem cells. The proliferation and upward migration of colony crypt daughter cells, and their differentiation into different epithelial cell types is regulated in part by Wnt/β-catenin signaling, suggesting its essential role in intestinal development and homeostasis. However, continuous activation of this signaling pathway in intestinal stem cells due to somatic mutations is a hallmark of most CRCs. Hence, targeting Wnt/β-catenin signaling in CSCs can be a focus of new treatment strategies. Curcumin, the effective compound of the plant Curcuma longa, has been studied as an anticancer agent. Recently, it has been shown that curcumin and its analogues can decrease the risk of tumor recurrence by targeting CSCs via various cell signaling pathways, in particular the Wnt/β-catenin pathway. In this review, we shall describe the relationship between Wnt-regulated CSCs and progression of CRC, and the efficacy of curcumin and its analogues in targeting colorectal CSCs and the Wnt/β-catenin molecular pathway involved.