Curcumin suppresses colorectal cancer progression through down-regulation of Wnt signaling in cancer stem cells
AbstractColorectal cancer (CRC) is a leading cause of death worldwide. Despite improved treatment procedures, the disease rarely can be cured completely mainly because of recurrence. It is well evident that cancer recurrence is caused by cancer stem cells (CSCs), rare and immortal cells that can initiate and develop tumors and protect them against anticancer agents. CSCs are generated as a result of failures in intracellular signaling pathways of which Wnt/β-catenin has a key role in CRC. The Wnt/β-catenin signaling pathway is thought to be the major signaling in the maintenance of homeostasis of intestinal stem cells. Proliferation, upward migration of the colony crypt daughter cells, and differentiation into all epithelial cell types at least in part is regulated by Wnt/β-catenin signaling, suggesting its essential role during 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 plant Curcuma longa, has been studied as an anticancer agent. Recently, it has been shown that curcumin and its analogues decrease the risk of tumor recurrence by targeting CSCs via various cell signaling, in particular, Wnt/β-catenin pathway. In this review, we describe a relationship between Wnt-regulated CSCs and progression of CRC and the efficacy of curcumin and its analogues in targeting colorectal CSCs and also the Wnt/β-catenin molecular pathway involved.
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