HMDB and 5-AzadC combination reverses tumor suppressor CCAAT/enhancer-binding protein delta to strengthen the death of liver cancer cells

Chien Feng Li, Hsin Hwa Tsai, Chiung Yuan Ko, Yen Chun Pan, Chia Jui Yen, Hong Yue Lai, Chiou Hwa Yuh, Wan Chen Wu, Ju Ming Wang

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7 Citations (Scopus)


Hepatocellular carcinoma (HCC) can arise from chronic inflammation due to viral infection, organ damage, drug toxicity, or alcohol abuse. Moreover, gene desensitization via aberrant CpG island methylation is a frequent epigenetic defect in HCC. However, the details of how inflammation is linked with epigenetic-mediated desensitization of tumor suppressor genes remains less investigated. In this study, we found that loss of CEBPD enhances the growth of liver cancer cells and is associated with the occurrence of liver cancers, as determined by the assessment of clinical specimens and in vivo animal models. Moreover, E2F1-regulated epigenetic axis attenuated CEBPD expression in liver cancer cells. CEBPD is responsive to the hydroxymethyldibenzoylmethane (HMDB)-induced p38/ CREB pathway and plays an important role in the HMDBinduced apoptosis of cancer cells. Regarding depression of epigenetic effects to enhance HMDB-induced CEBPD expression, the combination of HMDB and 5-Aza-2′-deoxycytidine (5-AzadC) could enhance the death of liver cancer cells and reduce the tumor formation of Huh7 xenograft mice. In conclusion, these results suggest that CEBPD could be a useful diagnostic marker and therapeutic target in HCC. The results also reveal the therapeutic potential for low-dose 5-AzadC to enhance the HMDB-induced death of HCC cells.

Original languageEnglish
Pages (from-to)2623-2633
Number of pages11
JournalMolecular Cancer Therapeutics
Issue number11
Publication statusPublished - Nov 1 2015


ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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