摘要

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.
原文英語
頁(從 - 到)1227-1237
頁數11
期刊American Journal of Cancer Research
7
發行號5
出版狀態已發佈 - 2017

指紋

Neoplastic Stem Cells
trichostatin A
Colonic Neoplasms
Colon
Carcinogenesis
Fluorouracil
Side-Population Cells
Catenins
Histone Deacetylase Inhibitors
Antifungal Agents
Developed Countries
Drug Resistance
Stem Cells
Neoplasm Metastasis
Cell Line
Mortality
Population
Neoplasms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

引用此文

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title = "The identification and validation of Trichosstatin A as a potential inhibitor of colon tumorigenesis and colon cancer stem-like cells",
abstract = "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.",
keywords = "5-FU resistance, Cancer stem-like cells, Colon cancer, Drug resistance, Side-population cells, Trichostatin A (TSA)",
author = "Huang, {Tse Hung} and Wu, {Szu Yuan} and Huang, {Yan Jiun} and Wei, {Po Li} and Wu, {Alexander T.H.} and Chao, {Tsu Yi}",
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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)

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