TY - JOUR
T1 - Targeting colon cancer stem cells using a new curcumin analogue, GO-Y030
AU - Lin, L.
AU - Liu, Y.
AU - Li, H.
AU - Li, P. K.
AU - Fuchs, J.
AU - Shibata, H.
AU - Iwabuchi, Y.
AU - Lin, J.
N1 - Funding Information:
This research was partly supported by fund from NIH R03CA137479-01A1 to Jiayuh Lin and supported by National Natural Science Foundation of China (81001005) to Li Lin. We acknowledge Cynthia McAllister and David Dunaway at the Flow Cytometry Core of Nationwide Children’s Hospital for running flow cytometry assay. We thank David Jou for reading the manuscript.
PY - 2011/7/12
Y1 - 2011/7/12
N2 - 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.
AB - 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.
KW - ALDH
KW - cancer stem cells
KW - CD133
KW - colon cancer
KW - curcumin analogue
KW - STAT3
UR - http://www.scopus.com/inward/record.url?scp=79960276970&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79960276970&partnerID=8YFLogxK
U2 - 10.1038/bjc.2011.200
DO - 10.1038/bjc.2011.200
M3 - Article
C2 - 21694723
AN - SCOPUS:79960276970
SN - 0007-0920
VL - 105
SP - 212
EP - 220
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 2
ER -
