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Depletion of HDAC1, 7 and 8 by Histone Deacetylase Inhibition Confers Elimination of Pancreatic Cancer Stem Cells in Combination with Gemcitabine
by
Ying, Yin
, Yan, Shi-Li
, Sun, Ze
, Cai, Mao-Hua
, Wang, Bai-Kui
, Xu, Xiao-Gang
, Tu, Yue-Xing
in
13/100
/ 13/2
/ 13/31
/ 13/51
/ 13/89
/ 631/154/556
/ 631/67/71
/ Antimetabolites, Antineoplastic - metabolism
/ Apoptosis
/ Cell growth
/ Cell Line, Tumor
/ Cell proliferation
/ Cell Survival - drug effects
/ Chromatin
/ Deactivation
/ Deoxycytidine - analogs & derivatives
/ Deoxycytidine - metabolism
/ E-cadherin
/ Gemcitabine
/ Histone deacetylase
/ Histone Deacetylase Inhibitors - metabolism
/ Histone Deacetylases - metabolism
/ Humanities and Social Sciences
/ Humans
/ Hydroxamic Acids - metabolism
/ Lysine
/ mRNA
/ multidisciplinary
/ Neoplastic Stem Cells - drug effects
/ Neoplastic Stem Cells - physiology
/ Oct-4 protein
/ Pancreatic cancer
/ Pancreatic Neoplasms - pathology
/ Science
/ Science (multidisciplinary)
/ siRNA
/ Stem cells
/ Trichostatin A
/ Tumor suppressor genes
/ Vimentin
2018
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Depletion of HDAC1, 7 and 8 by Histone Deacetylase Inhibition Confers Elimination of Pancreatic Cancer Stem Cells in Combination with Gemcitabine
by
Ying, Yin
, Yan, Shi-Li
, Sun, Ze
, Cai, Mao-Hua
, Wang, Bai-Kui
, Xu, Xiao-Gang
, Tu, Yue-Xing
in
13/100
/ 13/2
/ 13/31
/ 13/51
/ 13/89
/ 631/154/556
/ 631/67/71
/ Antimetabolites, Antineoplastic - metabolism
/ Apoptosis
/ Cell growth
/ Cell Line, Tumor
/ Cell proliferation
/ Cell Survival - drug effects
/ Chromatin
/ Deactivation
/ Deoxycytidine - analogs & derivatives
/ Deoxycytidine - metabolism
/ E-cadherin
/ Gemcitabine
/ Histone deacetylase
/ Histone Deacetylase Inhibitors - metabolism
/ Histone Deacetylases - metabolism
/ Humanities and Social Sciences
/ Humans
/ Hydroxamic Acids - metabolism
/ Lysine
/ mRNA
/ multidisciplinary
/ Neoplastic Stem Cells - drug effects
/ Neoplastic Stem Cells - physiology
/ Oct-4 protein
/ Pancreatic cancer
/ Pancreatic Neoplasms - pathology
/ Science
/ Science (multidisciplinary)
/ siRNA
/ Stem cells
/ Trichostatin A
/ Tumor suppressor genes
/ Vimentin
2018
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Depletion of HDAC1, 7 and 8 by Histone Deacetylase Inhibition Confers Elimination of Pancreatic Cancer Stem Cells in Combination with Gemcitabine
by
Ying, Yin
, Yan, Shi-Li
, Sun, Ze
, Cai, Mao-Hua
, Wang, Bai-Kui
, Xu, Xiao-Gang
, Tu, Yue-Xing
in
13/100
/ 13/2
/ 13/31
/ 13/51
/ 13/89
/ 631/154/556
/ 631/67/71
/ Antimetabolites, Antineoplastic - metabolism
/ Apoptosis
/ Cell growth
/ Cell Line, Tumor
/ Cell proliferation
/ Cell Survival - drug effects
/ Chromatin
/ Deactivation
/ Deoxycytidine - analogs & derivatives
/ Deoxycytidine - metabolism
/ E-cadherin
/ Gemcitabine
/ Histone deacetylase
/ Histone Deacetylase Inhibitors - metabolism
/ Histone Deacetylases - metabolism
/ Humanities and Social Sciences
/ Humans
/ Hydroxamic Acids - metabolism
/ Lysine
/ mRNA
/ multidisciplinary
/ Neoplastic Stem Cells - drug effects
/ Neoplastic Stem Cells - physiology
/ Oct-4 protein
/ Pancreatic cancer
/ Pancreatic Neoplasms - pathology
/ Science
/ Science (multidisciplinary)
/ siRNA
/ Stem cells
/ Trichostatin A
/ Tumor suppressor genes
/ Vimentin
2018
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Depletion of HDAC1, 7 and 8 by Histone Deacetylase Inhibition Confers Elimination of Pancreatic Cancer Stem Cells in Combination with Gemcitabine
Journal Article
Depletion of HDAC1, 7 and 8 by Histone Deacetylase Inhibition Confers Elimination of Pancreatic Cancer Stem Cells in Combination with Gemcitabine
2018
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Overview
Trichostatin A (TSA) possess histone deacetylase (HDAC) inhibitory potential, can reverse the deactivation of tumor suppressor genes and inhibit tumor cell proliferation. We evaluated the effect of TSA on HDAC expression, tumor cell proliferation, and cancer stem cells (CSCs) activities in pancreatic ductal adenocarnoma (PDAC) cells. The PDAC cell lines MiaPaCa-2 and PANC-1 were distinctly sensitive to TSA, with enhanced apoptosis, compared to SAHA. TSA or SAHA inhibited vimentin, HDACs 1, 7 and 8, upregulated E-cadherin mRNA and protein levels in the PDAC cells, and time-dependently downregulated Oct-4, Sox-2, and Nanog, as well as inhibited PDAC tumorsphere formation. TSA also induces accumulation of acetylated histones, while increasing histone 3 lysine 4 or 9 dimethylation levels in PDAC cells and enhancing the epigenetic activity of SAHA. The anti-CSCs effect of TSA was like that obtained by silencing HDAC-1 or 7 using siRNA, and enhances Gemcitabine activity. Our study highlights the molecular targetability of HDACs 1, 7, and 8, confirm their PDAC-CSCs maintaining role, and demonstrate that compared to SAHA, TSA modulates the epigenetically- mediated oncogenic activity of PDAC-CSCs, and potentiate Gemcitabine therapeutic activity, making a case for further exploration of TSA activity alone or in combination with Gemcitabine in PDAC therapy.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/2
/ 13/31
/ 13/51
/ 13/89
/ Antimetabolites, Antineoplastic - metabolism
/ Cell Survival - drug effects
/ Deoxycytidine - analogs & derivatives
/ Histone Deacetylase Inhibitors - metabolism
/ Histone Deacetylases - metabolism
/ Humanities and Social Sciences
/ Humans
/ Hydroxamic Acids - metabolism
/ Lysine
/ mRNA
/ Neoplastic Stem Cells - drug effects
/ Neoplastic Stem Cells - physiology
/ Pancreatic Neoplasms - pathology
/ Science
/ siRNA
/ Vimentin
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