摘要
原文 | 英語 |
---|---|
頁(從 - 到) | 1227-1237 |
頁數 | 11 |
期刊 | American Journal of Cancer Research |
卷 | 7 |
發行號 | 5 |
出版狀態 | 已發佈 - 2017 |
指紋
ASJC Scopus subject areas
- Oncology
- Cancer Research
引用此文
The identification and validation of Trichosstatin A as a potential inhibitor of colon tumorigenesis and colon cancer stem-like cells. / Huang, Tse Hung; Wu, Szu Yuan; Huang, Yan Jiun; Wei, Po Li; Wu, Alexander T.H.; Chao, Tsu Yi.
於: American Journal of Cancer Research, 卷 7, 編號 5, 2017, p. 1227-1237.研究成果: 雜誌貢獻 › 文章
}
TY - JOUR
T1 - The identification and validation of Trichosstatin A as a potential inhibitor of colon tumorigenesis and colon cancer stem-like cells
AU - Huang, Tse Hung
AU - Wu, Szu Yuan
AU - Huang, Yan Jiun
AU - Wei, Po Li
AU - Wu, Alexander T.H.
AU - Chao, Tsu Yi
PY - 2017
Y1 - 2017
N2 - Colon cancer is one of the most prevalent cancer types in developed countries. Metastasis and drug resistance are two contributing factors to the high mortality rate. Accumulating evidence suggest that cancer stem-like cells (CSCs) represents as a major contributor to these malignant features. Here, we identified and isolated colon cancer stem-like cells using side-population (SP) method from human colon cancer cell lines. SP colon cells demonstrate cancer stem-like cell properties including enhanced sphere-forming ability and resistance towards fluorouracil (5-FU). The CSC properties were associated with the increased expression level of major oncogenic and stem cell markers including β-catenin, NF-κB, Akt/mTOR, KRAS and c-Myc. Trichostatin A (TSA), an antifungal antibiotic also a HDAC inhibitor, was found to function not only to decrease the expression of oncogenic markers but also the colon CSC properties. Importantly, TSA and 5-FU combined treatment synergistically suppressed colon cancer viability. Finally, in vivo results demonstrated that TSA alone and in combination with 5-FU effectively suppressed colon tumorigenesis. Collectively, this study provides preclinical evidence that TSA may function as a potential colon cancer therapeutic agent by targeting CSC and overcoming 5-FU resistance.
AB - Colon cancer is one of the most prevalent cancer types in developed countries. Metastasis and drug resistance are two contributing factors to the high mortality rate. Accumulating evidence suggest that cancer stem-like cells (CSCs) represents as a major contributor to these malignant features. Here, we identified and isolated colon cancer stem-like cells using side-population (SP) method from human colon cancer cell lines. SP colon cells demonstrate cancer stem-like cell properties including enhanced sphere-forming ability and resistance towards fluorouracil (5-FU). The CSC properties were associated with the increased expression level of major oncogenic and stem cell markers including β-catenin, NF-κB, Akt/mTOR, KRAS and c-Myc. Trichostatin A (TSA), an antifungal antibiotic also a HDAC inhibitor, was found to function not only to decrease the expression of oncogenic markers but also the colon CSC properties. Importantly, TSA and 5-FU combined treatment synergistically suppressed colon cancer viability. Finally, in vivo results demonstrated that TSA alone and in combination with 5-FU effectively suppressed colon tumorigenesis. Collectively, this study provides preclinical evidence that TSA may function as a potential colon cancer therapeutic agent by targeting CSC and overcoming 5-FU resistance.
KW - 5-FU resistance
KW - Cancer stem-like cells
KW - Colon cancer
KW - Drug resistance
KW - Side-population cells
KW - Trichostatin A (TSA)
UR - http://www.scopus.com/inward/record.url?scp=85019901203&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85019901203&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:85019901203
VL - 7
SP - 1227
EP - 1237
JO - American Journal of Cancer Research
JF - American Journal of Cancer Research
SN - 2156-6976
IS - 5
ER -