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

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.

• Authors: L Lin, Y Liu, H Li, P-K Li, J Fuchs, H Shibata, Y Iwabuchi, J Lin
• Journal: British journal of cancer (Br J Cancer) Vol. 105 Issue 2 Pg. 212-20 (Jul 12 2011) ISSN: 1532-1827 [Electronic] England
• PMID: 21694723 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• 1,5-bis(3,5-bis(methoxymethoxy)phenyl)penta-1,4-dien-3-one
• Antineoplastic Agents
• Benzene Derivatives
• Ketones
• Curcumin

Topics

• Animals
• Antineoplastic Agents (administration & dosage, pharmacology, therapeutic use)
• Benzene Derivatives (administration & dosage, pharmacology, therapeutic use)
• Carcinoma (drug therapy, pathology)
• Cell Line, Tumor
• Colonic Neoplasms (drug therapy, pathology)
• Curcumin (analogs & derivatives, pharmacology)
• Drug Delivery Systems (methods)
• Female
• HCT116 Cells
• HT29 Cells
• Humans
• Ketones (administration & dosage, pharmacology, therapeutic use)
• Mice
• Mice, Inbred NOD
• Mice, SCID
• Neoplastic Stem Cells (drug effects, pathology)
• Xenograft Model Antitumor Assays