Medical College of Wisconsin
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Suberoylanilide hydroxamic Acid, a histone deacetylase inhibitor, alters multiple signaling pathways in hepatocellular carcinoma cell lines. Am J Surg 2017 Apr;213(4):645-651

Date

12/23/2016

Pubmed ID

28007318

DOI

10.1016/j.amjsurg.2016.12.001

Scopus ID

2-s2.0-85008402646 (requires institutional sign-in at Scopus site)   8 Citations

Abstract

INTRODUCTION: Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, has preclinical efficacy in hepatocellular carcinoma (HCC), despite an unclear molecular mechanism. We sought to further investigate the effects of SAHA on HCC. We hypothesize SAHA will inhibit HCC cellular proliferation through apoptosis and aid in further profiling SAHA's effect on HCC oncogenic pathways.

METHODS: HCC cell lines were treated with various concentrations of SAHA. Cell proliferation was determined by MTT and colonogenic assays. Cell lysates were analyzed via Western blotting for apoptotic and oncogenic pathway markers. Caspase glo-3/7 was used to assess apoptosis.

RESULTS: SAHA treatment demonstrated significant (<0.05) reduction in cell growth and colony formation through apoptosis and cell cycle arrest. Western analysis showed reduction in Notch, pAKT and pERK1/2 proteins. Interestingly, phosphorylated STAT3 was increased in all cell lines.

CONCLUSIONS: SAHA inhibits Notch, AKT, and Raf-1 pathways but not the STAT3 pathway. We believe that STAT3 may lead to cancer cell progression, reducing SAHA efficacy in HCC. Therefore, combination of SAHA and STAT or Notch inhibition may be a strategy for HCC treatment.

Author List

Kunnimalaiyaan S, Sokolowski K, Gamblin TC, Kunnimalaiyaan M

Author

Thomas Clark Gamblin MD Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Apoptosis
Carcinoma, Hepatocellular
Caspase 3
Caspase 7
Cell Cycle
Cell Line, Tumor
Cell Proliferation
Cell Survival
Histone Deacetylase Inhibitors
Humans
Hydroxamic Acids
Liver Neoplasms
MAP Kinase Signaling System
Oncogene Protein v-akt
Protein Isoforms
Receptors, Notch
STAT3 Transcription Factor