Autophagy potentiates the anti-cancer effects of the histone deacetylase inhibitors in hepatocellular carcinoma

Yuan Ling Liu, Pei Ming Yang, Chia Tung Shun, Ming Shiang Wu, Jing Ru Weng, Ching Chow Chen

Research output: Contribution to journalArticle

123 Citations (Scopus)

Abstract

Hepatocellular carcinoma (HCC ) is the fifth most common cancer and the third leading cause of cancer death worldwide. Drug treatments for HCC have been largely unsuccessful. Histone deacetylase inhibitors can reactivate tumor suppressor genes in cancer cells and serve as potential anti-cancer drugs. Two potent HDAC inhibitors OSU-HDAC42 and SAHA induced autophagy in HCC cells as revealed by transmission electron microscopy, immunofluorescence and LC3-II accumulation. We found that SAHA and OSU-HDAC42 induced autophagy through downregulation of Akt/mTOR signaling and induction of ER stress response. Inhibition of autophagy by 3-MA or Atg5 knockout reduced SAHA-induced cytotoxicity, indicating that SAHA-induced autophagy led to cell death. Our results show that the combination of autophagy inducers with SAHA might be attractive for the treatment of HCC and pharmacological targeting of autophagy provides promise for the management of cancer therapy.

Original languageEnglish
Pages (from-to)1057-1065
Number of pages9
JournalAutophagy
Volume6
Issue number8
DOIs
Publication statusPublished - Nov 16 2010
Externally publishedYes

Fingerprint

Histone Deacetylase Inhibitors
Autophagy
Hepatocellular Carcinoma
Neoplasms
Tumor Suppressor Genes
Transmission Electron Microscopy
Pharmaceutical Preparations
Fluorescent Antibody Technique
Cause of Death
Cell Death
Therapeutics
Down-Regulation
Pharmacology

Keywords

  • Apoptosis
  • Autophagy
  • ER stress
  • Hepatocellular carcinoma
  • Histone deacetylase inhibitor

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Autophagy potentiates the anti-cancer effects of the histone deacetylase inhibitors in hepatocellular carcinoma. / Liu, Yuan Ling; Yang, Pei Ming; Shun, Chia Tung; Wu, Ming Shiang; Weng, Jing Ru; Chen, Ching Chow.

In: Autophagy, Vol. 6, No. 8, 16.11.2010, p. 1057-1065.

Research output: Contribution to journalArticle

Liu, Yuan Ling ; Yang, Pei Ming ; Shun, Chia Tung ; Wu, Ming Shiang ; Weng, Jing Ru ; Chen, Ching Chow. / Autophagy potentiates the anti-cancer effects of the histone deacetylase inhibitors in hepatocellular carcinoma. In: Autophagy. 2010 ; Vol. 6, No. 8. pp. 1057-1065.
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