Sonic hedgehog and Wnt/ß-catenin pathways mediate curcumin inhibition of breast cancer stem cells.

ABSTRACT

Cancer stem cells (CSCs) play an essential role in the progression of many tumors. Sonic hedgehog (Shh) and Wnt/ß-catenin pathways are crucial in maintaining the stemness of CSCs. Curcumin has been shown to possess anticancer activity. However, the interventional effect of curcumin on breast CSCs has not been elucidated. In the present study, we investigated the role of Shh and Wnt/ß-catenin pathway in curcumin inhibition of breast CSCs. We showed that the levels of breast CSCs markers were significantly elevated in SUM159 and MCF7 sphere-forming cells. We further illustrated that curcumin effectively decreased breast CSCs activity by inhibiting tumor sphere formation, decreasing breast CSCs markers (CD44, ALDH1A1, Nanog, and Oct4), as well as inhibiting proliferation and inducing apoptosis. Moreover, we showed that downregulation of Shh and Wnt/ß-catenin activity resulted in breast CSCs inhibition; curcumin exerted an inhibitory effect on breast CSCs by suppressing both Shh and Wnt/ß-catenin pathways. Taken together, these results indicated curcumin inhibition of breast CSCs by downregulation of Shh and Wnt/ß-catenin pathways. Findings from this study could provide new insights into the potential therapeutic application of curcumin in breast CSCs elimination and cancer intervention.