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

L. Lin, Y. Liu, H. Li, P. K. Li, J. Fuchs, H. Shibata, Y. Iwabuchi, J. Lin

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)212-220
Number of pages9
JournalBritish Journal of Cancer
Volume105
Issue number2
DOIs
Publication statusPublished - 2011 Jul 12

Keywords

  • ALDH
  • CD133
  • STAT3
  • cancer stem cells
  • colon cancer
  • curcumin analogue

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Lin, L., Liu, Y., Li, H., Li, P. K., Fuchs, J., Shibata, H., Iwabuchi, Y., & Lin, J. (2011). Targeting colon cancer stem cells using a new curcumin analogue, GO-Y030. British Journal of Cancer, 105(2), 212-220. https://doi.org/10.1038/bjc.2011.200