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HDAC Screening Identifies the HDAC Class I Inhibitor Romidepsin as a Promising Epigenetic Drug for Biliary Tract Cancer
by
Bekric, Dino
, Beyreis, Marlena
, Kiesslich, Tobias
, Erber, Sara
, Ritter, Markus
, Winkelmann, Paul
, Neumayer, Bettina
, Neureiter, Daniel
, Mayr, Christian
, Klieser, Eckhard
, Jäger, Tarkan
, Dobias, Heidemarie
in
Acetylation
/ Angiogenesis
/ Apoptosis
/ Biliary tract
/ Cancer
/ Cell cycle
/ Cell death
/ Cell viability
/ Cisplatin
/ Cytotoxicity
/ Enzymes
/ Epigenetics
/ FDA approval
/ Gene expression
/ Histone deacetylase
/ Histones
/ Lymphoma
/ Lysine
/ Medical prognosis
/ Mutation
/ Patients
/ Proteins
/ Rare diseases
/ Tumorigenesis
/ Tumors
2021
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HDAC Screening Identifies the HDAC Class I Inhibitor Romidepsin as a Promising Epigenetic Drug for Biliary Tract Cancer
by
Bekric, Dino
, Beyreis, Marlena
, Kiesslich, Tobias
, Erber, Sara
, Ritter, Markus
, Winkelmann, Paul
, Neumayer, Bettina
, Neureiter, Daniel
, Mayr, Christian
, Klieser, Eckhard
, Jäger, Tarkan
, Dobias, Heidemarie
in
Acetylation
/ Angiogenesis
/ Apoptosis
/ Biliary tract
/ Cancer
/ Cell cycle
/ Cell death
/ Cell viability
/ Cisplatin
/ Cytotoxicity
/ Enzymes
/ Epigenetics
/ FDA approval
/ Gene expression
/ Histone deacetylase
/ Histones
/ Lymphoma
/ Lysine
/ Medical prognosis
/ Mutation
/ Patients
/ Proteins
/ Rare diseases
/ Tumorigenesis
/ Tumors
2021
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HDAC Screening Identifies the HDAC Class I Inhibitor Romidepsin as a Promising Epigenetic Drug for Biliary Tract Cancer
by
Bekric, Dino
, Beyreis, Marlena
, Kiesslich, Tobias
, Erber, Sara
, Ritter, Markus
, Winkelmann, Paul
, Neumayer, Bettina
, Neureiter, Daniel
, Mayr, Christian
, Klieser, Eckhard
, Jäger, Tarkan
, Dobias, Heidemarie
in
Acetylation
/ Angiogenesis
/ Apoptosis
/ Biliary tract
/ Cancer
/ Cell cycle
/ Cell death
/ Cell viability
/ Cisplatin
/ Cytotoxicity
/ Enzymes
/ Epigenetics
/ FDA approval
/ Gene expression
/ Histone deacetylase
/ Histones
/ Lymphoma
/ Lysine
/ Medical prognosis
/ Mutation
/ Patients
/ Proteins
/ Rare diseases
/ Tumorigenesis
/ Tumors
2021
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HDAC Screening Identifies the HDAC Class I Inhibitor Romidepsin as a Promising Epigenetic Drug for Biliary Tract Cancer
Journal Article
HDAC Screening Identifies the HDAC Class I Inhibitor Romidepsin as a Promising Epigenetic Drug for Biliary Tract Cancer
2021
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Overview
Inhibition of histone deacetylases (HDACs) is a promising anti-cancer approach. For biliary tract cancer (BTC), only limited therapeutic options are currently available. Therefore, we performed a comprehensive investigation of HDAC expression and pharmacological HDAC inhibition into a panel of eight established BTC cell lines. The screening results indicate a heterogeneous expression of HDACs across the studied cell lines. We next tested the effect of six established HDAC inhibitors (HDACi) covering pan- and class-specific HDACis on cell viability of BTC cells and found that the effect (i) is dose- and cell-line-dependent, (ii) does not correlate with HDAC isoform expression, and (iii) is most pronounced for romidepsin (a class I HDACi), showing the highest reduction in cell viability with IC50 values in the low-nM range. Further analyses demonstrated that romidepsin induces apoptosis in BTC cells, reduces HDAC activity, and increases acetylation of histone 3 lysine 9 (H3K9Ac). Similar to BTC cell lines, HDAC 1/2 proteins were heterogeneously expressed in a cohort of resected BTC specimens (n = 78), and their expression increased with tumor grading. The survival of BTC patients with high HDAC-2-expressing tumors was significantly shorter. In conclusion, HDAC class I inhibition in BTC cells by romidepsin is highly effective in vitro and encourages further in vivo evaluation in BTC. In situ assessment of HDAC 2 expression in BTC specimens indicates its importance for oncogenesis and/or progression of BTC as well as for the prognosis of BTC patients.
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