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

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单位: [1]Ohio State Univ, Nationwide Childrens Hosp, Coll Med, Dept Pediat,Res Inst,Ctr Childhood Canc, Columbus, OH 43205 USA [2]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Internal Med,Div Cardiol, Wuhan 430030, Peoples R China [3]Ohio State Univ, Coll Pharm, Div Med Chem & Pharmacognosy, Columbus, OH 43205 USA [4]Akita Univ, Grad Sch Med, Dept Clin Oncol, Akita 010, Japan [5]Tohoku Univ, Grad Sch Pharmaceut Sci, Dept Organ Chem, Sendai, Miyagi 9808578, Japan
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关键词: STAT3 curcumin analogue colon cancer cancer stem cells ALDH CD133

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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. British Journal of Cancer (2011) 105, 212-220. doi: 10.1038/bjc.2011.200 www.bjcancer.com Published online 21 June 2011 (C) 2011 Cancer Research UK

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出版当年[2010]版:
大类 | 2 区 医学
小类 | 3 区 肿瘤学
最新[2025]版:
大类 | 2 区 医学
小类 | 2 区 肿瘤学
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出版当年[2009]版:
Q1 ONCOLOGY
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Q1 ONCOLOGY

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第一作者单位: [1]Ohio State Univ, Nationwide Childrens Hosp, Coll Med, Dept Pediat,Res Inst,Ctr Childhood Canc, Columbus, OH 43205 USA [2]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Internal Med,Div Cardiol, Wuhan 430030, Peoples R China
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