Anticancer effects of suberoylanilide hydroxamic acid in esophageal squamous cancer cells in vitro and in vivo

C. Tzao, J. S. Jin, B. H. Chen, H. Y. Chung, C. C. Chang, T. Y. Hsu, G. H. Sun

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The effects of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, have not been studied in esophageal squamous cell cancer (ESCC). Cell viability assay; flow cytometry for cell cycle and annexin V apoptosis assays; assays for cell migration, invasion, and adhesion to extracellular matrix (ECM); and immunoblotting and immunofluorescence staining were performed in three ESCC cell lines. Tumor xenograft with semiquantitative immunohistochemistry was used to study the effects of SAHAin vivo. SAHA effectively inhibited growth of ESCC cells with half-inhibitory concentrations (IC50) ranging from 2.6 to 6.5μmol/L. SAHA restored acetylation of histone 3 lysine 9 (H3K9Ac) and histone 4 lysine 12 (H4K12Ac) with an induction of G1 or G2 cell cycle arrest and apoptosis. Expression of cell cycle checkpoint regulatory proteins including cyclin-dependent kinases (CDKs) and cyclins was decreased, whereas expression of cell cycle suppressors, p21, p27, and Rb was increased in ESCC cells after SAHA treatment. SAHA inhibited migration, invasion, and ECM adhesion in ESCC cells with an induction of E-cadherin expression. SAHA significantly inhibited growth of ESCC tumors with increased expression of p21, p27, Rb, and E-cadherin while decreasing expression of CDK4 and cyclin D1 within the murine tumors. In conclusion, SAHA had antigrowth activity against ESCC cells in vitro and in vivo while inhibiting cell migration, cell invasion, and ECM adhesion, suggesting its potential as an epigenetic therapeutic agent for ESCC.

Original languageEnglish
Pages (from-to)693-702
Number of pages10
JournalDiseases of the Esophagus
Volume27
Issue number7
DOIs
Publication statusPublished - 2014
Externally publishedYes

Fingerprint

Squamous Cell Neoplasms
Esophageal Neoplasms
Epithelial Cells
Extracellular Matrix
Cadherins
Histones
Lysine
Cell Movement
Cell Cycle
G2 Phase Cell Cycle Checkpoints
Apoptosis
G1 Phase Cell Cycle Checkpoints
Neoplasms
Cell Cycle Proteins
Cyclins
Histone Deacetylase Inhibitors
Cyclin-Dependent Kinases
vorinostat
In Vitro Techniques
Annexin A5

Keywords

  • Apoptosis
  • Cell cycle arrest
  • Esophageal squamous cell cancer
  • Histone deacetylase (HDAC)
  • Suberoylanilide hydroxamic acid (SAHA)

ASJC Scopus subject areas

  • Gastroenterology
  • Medicine(all)

Cite this

Anticancer effects of suberoylanilide hydroxamic acid in esophageal squamous cancer cells in vitro and in vivo. / Tzao, C.; Jin, J. S.; Chen, B. H.; Chung, H. Y.; Chang, C. C.; Hsu, T. Y.; Sun, G. H.

In: Diseases of the Esophagus, Vol. 27, No. 7, 2014, p. 693-702.

Research output: Contribution to journalArticle

Tzao, C. ; Jin, J. S. ; Chen, B. H. ; Chung, H. Y. ; Chang, C. C. ; Hsu, T. Y. ; Sun, G. H. / Anticancer effects of suberoylanilide hydroxamic acid in esophageal squamous cancer cells in vitro and in vivo. In: Diseases of the Esophagus. 2014 ; Vol. 27, No. 7. pp. 693-702.
@article{339f21faa2b24eb59c3b04947d1f1707,
title = "Anticancer effects of suberoylanilide hydroxamic acid in esophageal squamous cancer cells in vitro and in vivo",
abstract = "The effects of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, have not been studied in esophageal squamous cell cancer (ESCC). Cell viability assay; flow cytometry for cell cycle and annexin V apoptosis assays; assays for cell migration, invasion, and adhesion to extracellular matrix (ECM); and immunoblotting and immunofluorescence staining were performed in three ESCC cell lines. Tumor xenograft with semiquantitative immunohistochemistry was used to study the effects of SAHAin vivo. SAHA effectively inhibited growth of ESCC cells with half-inhibitory concentrations (IC50) ranging from 2.6 to 6.5μmol/L. SAHA restored acetylation of histone 3 lysine 9 (H3K9Ac) and histone 4 lysine 12 (H4K12Ac) with an induction of G1 or G2 cell cycle arrest and apoptosis. Expression of cell cycle checkpoint regulatory proteins including cyclin-dependent kinases (CDKs) and cyclins was decreased, whereas expression of cell cycle suppressors, p21, p27, and Rb was increased in ESCC cells after SAHA treatment. SAHA inhibited migration, invasion, and ECM adhesion in ESCC cells with an induction of E-cadherin expression. SAHA significantly inhibited growth of ESCC tumors with increased expression of p21, p27, Rb, and E-cadherin while decreasing expression of CDK4 and cyclin D1 within the murine tumors. In conclusion, SAHA had antigrowth activity against ESCC cells in vitro and in vivo while inhibiting cell migration, cell invasion, and ECM adhesion, suggesting its potential as an epigenetic therapeutic agent for ESCC.",
keywords = "Apoptosis, Cell cycle arrest, Esophageal squamous cell cancer, Histone deacetylase (HDAC), Suberoylanilide hydroxamic acid (SAHA)",
author = "C. Tzao and Jin, {J. S.} and Chen, {B. H.} and Chung, {H. Y.} and Chang, {C. C.} and Hsu, {T. Y.} and Sun, {G. H.}",
year = "2014",
doi = "10.1111/dote.12127",
language = "English",
volume = "27",
pages = "693--702",
journal = "Diseases of the Esophagus",
issn = "1120-8694",
publisher = "Wiley-Blackwell",
number = "7",

}

TY - JOUR

T1 - Anticancer effects of suberoylanilide hydroxamic acid in esophageal squamous cancer cells in vitro and in vivo

AU - Tzao, C.

AU - Jin, J. S.

AU - Chen, B. H.

AU - Chung, H. Y.

AU - Chang, C. C.

AU - Hsu, T. Y.

AU - Sun, G. H.

PY - 2014

Y1 - 2014

N2 - The effects of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, have not been studied in esophageal squamous cell cancer (ESCC). Cell viability assay; flow cytometry for cell cycle and annexin V apoptosis assays; assays for cell migration, invasion, and adhesion to extracellular matrix (ECM); and immunoblotting and immunofluorescence staining were performed in three ESCC cell lines. Tumor xenograft with semiquantitative immunohistochemistry was used to study the effects of SAHAin vivo. SAHA effectively inhibited growth of ESCC cells with half-inhibitory concentrations (IC50) ranging from 2.6 to 6.5μmol/L. SAHA restored acetylation of histone 3 lysine 9 (H3K9Ac) and histone 4 lysine 12 (H4K12Ac) with an induction of G1 or G2 cell cycle arrest and apoptosis. Expression of cell cycle checkpoint regulatory proteins including cyclin-dependent kinases (CDKs) and cyclins was decreased, whereas expression of cell cycle suppressors, p21, p27, and Rb was increased in ESCC cells after SAHA treatment. SAHA inhibited migration, invasion, and ECM adhesion in ESCC cells with an induction of E-cadherin expression. SAHA significantly inhibited growth of ESCC tumors with increased expression of p21, p27, Rb, and E-cadherin while decreasing expression of CDK4 and cyclin D1 within the murine tumors. In conclusion, SAHA had antigrowth activity against ESCC cells in vitro and in vivo while inhibiting cell migration, cell invasion, and ECM adhesion, suggesting its potential as an epigenetic therapeutic agent for ESCC.

AB - The effects of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, have not been studied in esophageal squamous cell cancer (ESCC). Cell viability assay; flow cytometry for cell cycle and annexin V apoptosis assays; assays for cell migration, invasion, and adhesion to extracellular matrix (ECM); and immunoblotting and immunofluorescence staining were performed in three ESCC cell lines. Tumor xenograft with semiquantitative immunohistochemistry was used to study the effects of SAHAin vivo. SAHA effectively inhibited growth of ESCC cells with half-inhibitory concentrations (IC50) ranging from 2.6 to 6.5μmol/L. SAHA restored acetylation of histone 3 lysine 9 (H3K9Ac) and histone 4 lysine 12 (H4K12Ac) with an induction of G1 or G2 cell cycle arrest and apoptosis. Expression of cell cycle checkpoint regulatory proteins including cyclin-dependent kinases (CDKs) and cyclins was decreased, whereas expression of cell cycle suppressors, p21, p27, and Rb was increased in ESCC cells after SAHA treatment. SAHA inhibited migration, invasion, and ECM adhesion in ESCC cells with an induction of E-cadherin expression. SAHA significantly inhibited growth of ESCC tumors with increased expression of p21, p27, Rb, and E-cadherin while decreasing expression of CDK4 and cyclin D1 within the murine tumors. In conclusion, SAHA had antigrowth activity against ESCC cells in vitro and in vivo while inhibiting cell migration, cell invasion, and ECM adhesion, suggesting its potential as an epigenetic therapeutic agent for ESCC.

KW - Apoptosis

KW - Cell cycle arrest

KW - Esophageal squamous cell cancer

KW - Histone deacetylase (HDAC)

KW - Suberoylanilide hydroxamic acid (SAHA)

UR - http://www.scopus.com/inward/record.url?scp=84906790199&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84906790199&partnerID=8YFLogxK

U2 - 10.1111/dote.12127

DO - 10.1111/dote.12127

M3 - Article

C2 - 24033428

AN - SCOPUS:84906790199

VL - 27

SP - 693

EP - 702

JO - Diseases of the Esophagus

JF - Diseases of the Esophagus

SN - 1120-8694

IS - 7

ER -