Curcumin attenuates resistance to irinotecan via induction of apoptosis of cancer stem cells in chemoresistant colon cancer cells

Resistance to conventional chemotherapeutic agents, including irinotecan (CPT-11), 5-fluorouracil and capecitabine is a major cause for therapeutic failure in patients with colorectal cancer (CRC). Increasing evidence has demonstrated that cancer cells exhibiting stem cell-like characteristics are associated with the development of resistance to chemotherapeutic agents. As a plant polyphenol, curcumin has been demonstrated to have the ability to ameliorate resistance of CRC to chemotherapeutic agents, but the associations among curcumin, cancer stem cells (CSCs) and chemoresistance of CRC remain unclear. The present study established a CPT-11-resistant colon cancer cell line, LoVo/CPT-11 cells, and detected the expression levels of CSC identification markers [cluster of differentiation (CD)44, CD133, epithelial cell adhesion molecule (EpCAM) and CD24] in parental cells and CPT-11-resistant cells. It was revealed that the expression levels of the colon CSC markers in LoVo/CPT-11 cells were significantly higher compared those in parental cells at the mRNA and protein level. The effect of curcumin on the chemoresistance to CPT-11 and the expression levels of CSC identification markers in LoVo/CPT-11 cells separately treated with curcumin and CPT-11 were further investigated. The results revealed that curcumin significantly attenuated chemoresistance to CPT-11, and treatment with curcumin resulted in a significant reduction of the expression levels of CSC identification markers. Furthermore, a tumor sphere formation assay was used to enrich colon CSCs from LoVo/CPT-11 cells, and demonstrated that curcumin efficiently diminished the traits of colon CSCs, as evidenced by the inability to form tumor spheres, the reduction in the expression of CSC identification markers, and apoptosis-induced effects on sphere-forming cells treated with curcumin alone or in combination with CPT-11. Altogether, the present data demonstrated that curcumin attenuated resistance to chemotherapeutic drugs through induction of apoptosis of CSCs among colon cancer cells. These findings may provide novel evidence for the therapeutic application of curcumin in CRC intervention.