HMDB and 5-AzadC Combination Reverses Tumor Suppressor CCAAT/Enhancer-Binding Protein Delta to Strengthen the Death of Liver Cancer Cells.

Abstract:

: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 HMDB-induced 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.

journal_name

Mol Cancer Ther

authors

Li CF,Tsai HH,Ko CY,Pan YC,Yen CJ,Lai HY,Yuh CH,Wu WC,Wang JM

doi

10.1158/1535-7163.MCT-15-0025

subject

Has Abstract

pub_date

2015-11-01 00:00:00

pages

2623-33

issue

11

eissn

1535-7163

issn

1538-8514

pii

1535-7163.MCT-15-0025

journal_volume

14

pub_type

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