摘要:BACKGROUND/OBJECTIVES
Colorectal cancer (CRC) is the third most common cancer worldwide and has a high recurrence rate, which is associated with cancer stem cells (CSCs). β-carotene (BC) possesses antioxidant activity and several anticancer mechanisms. However, no investigation has examined its effect on colon cancer stemness.
MATERIALS/METHODS
CD133
+CD44
+ HCT116 and CD133
+CD44
+ HT-29 cells were isolated and analyzed their self-renewal capacity by clonogenic and sphere formation assays. Expressions of several CSCs markers and Wnt/β-catenin signaling were examined. In addition, CD133
+CD44
+ HCT116 cells were subcutaneously injected in xenograft mice and analyzed the effect of BC on tumor formation, tumor volume, and CSCs markers in tumors.
RESULTS
BC inhibited self-renewal capacity and CSC markers, including
CD44,
CD133,
ALDH1A1,
NOTCH1, Sox2, and β-catenin
in vitro. The effects of BC on CSC markers were confirmed in primary cells isolated from human CRC tumors. BC supplementation decreased the number and size of tumors and delayed the tumor-onset time in xenograft mice injected with CD133
+CD44
+ HCT116 cells. The inhibitory effect of BC on CSC markers and the Wnt/β-catenin signaling pathway in tumors was confirmed
in vivo as well.
CONCLUSIONS
These results suggest that BC may be a potential therapeutic agent for colon cancer by targeting colon CSCs.