Targeting colon cancer stem cells using a new curcumin analogue, GO-Y030.

Lin L, Liu Y, Li H, Li PK, Fuchs J, Shibata H, Iwabuchi Y, Lin J
Br J Cancer. 2011 105 (2): 212-20

PMID: 21694723 · PMCID: PMC3142799 · DOI:10.1038/bjc.2011.200

BACKGROUND - Persistent activation of signal transducers and activators of transcription 3 (STAT3) is commonly detected in many types of cancer, including colon cancer. To date, whether STAT3 is activated and the effects of STAT3 inhibition by a newly developed curcumin analogue, GO-Y030, in colon cancer stem cells are still unknown.

METHODS - Flow cytometry was used to isolate colon cancer stem cells, which are characterised by both aldehyde dehydrogenase (ALDH)-positive and CD133-positive subpopulations (ALDH(+)/CD133(+)). The levels of STAT3 phosphorylation and the effects of STAT3 inhibition by a newly developed curcumin analogue, GO-Y030, that targets STAT3 in colon cancer stem cells were examined.

RESULTS - Our results observed that ALDH(+)/CD133(+) colon cancer cells expressed higher levels of phosphorylated STAT3 than ALDH-negative/CD133-negative colon cancer cells, suggesting that STAT3 is activated in colon cancer stem cells. GO-Y030 and curcumin inhibited STAT3 phosphorylation, cell viability, tumoursphere formation in colon cancer stem cells. GO-Y030 also reduced STAT3 downstream target gene expression and induced apoptosis in colon cancer stem cells. Furthermore, GO-Y030 suppressed tumour growth of cancer stem cells from both SW480 and HCT-116 colon cancer cell lines in the mouse model.

CONCLUSION - Our results indicate that STAT3 is a novel therapeutic target in colon cancer stem cells, and inhibition of activated STAT3 in cancer stem cells by GO-Y030 may offer an effective treatment for colorectal cancer.

MeSH Terms (18)

Animals Antineoplastic Agents Benzene Derivatives Carcinoma Cell Line, Tumor Colonic Neoplasms Curcumin Drug Delivery Systems Female HCT116 Cells HT29 Cells Humans Ketones Mice Mice, Inbred NOD Mice, SCID Neoplastic Stem Cells Xenograft Model Antitumor Assays

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