TY - JOUR
T1 - HMDB and 5-AzadC combination reverses tumor suppressor CCAAT/enhancer-binding protein delta to strengthen the death of liver cancer cells
AU - Li, Chien Feng
AU - Tsai, Hsin Hwa
AU - Ko, Chiung Yuan
AU - Pan, Yen Chun
AU - Yen, Chia Jui
AU - Lai, Hong Yue
AU - Yuh, Chiou Hwa
AU - Wu, Wan Chen
AU - Wang, Ju Ming
PY - 2015/11/1
Y1 - 2015/11/1
N2 - 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.
AB - 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.
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U2 - 10.1158/1535-7163.MCT-15-0025
DO - 10.1158/1535-7163.MCT-15-0025
M3 - Article
C2 - 26358750
AN - SCOPUS:84958164701
SN - 1535-7163
VL - 14
SP - 2623
EP - 2633
JO - Molecular Cancer Therapeutics
JF - Molecular Cancer Therapeutics
IS - 11
ER -