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

研究成果: 雜誌貢獻文章

6 引文 (Scopus)

摘要

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.
原文英語
頁(從 - 到)2623-2633
頁數11
期刊Molecular Cancer Therapeutics
14
發行號11
DOIs
出版狀態已發佈 - 十一月 1 2015

指紋

decitabine
CCAAT-Enhancer-Binding Protein-delta
Tumor Suppressor Proteins
Liver Neoplasms
Epigenomics
Hepatocellular Carcinoma
Inflammation
CpG Islands
Virus Diseases
Drug-Related Side Effects and Adverse Reactions
Tumor Suppressor Genes
Heterografts
Methylation
Alcoholism
Substance-Related Disorders
Neoplasms
Animal Models
Apoptosis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

引用此文

HMDB and 5-AzadC combination reverses tumor suppressor CCAAT/enhancer-binding protein delta to strengthen the death of liver cancer cells. / Li, Chien Feng; Tsai, Hsin Hwa; Ko, Chiung Yuan; Pan, Yen Chun; Yen, Chia Jui; Lai, Hong Yue; Yuh, Chiou Hwa; Wu, Wan Chen; Wang, Ju Ming.

於: Molecular Cancer Therapeutics, 卷 14, 編號 11, 01.11.2015, p. 2623-2633.

研究成果: 雜誌貢獻文章

Li, Chien Feng ; Tsai, Hsin Hwa ; Ko, Chiung Yuan ; Pan, Yen Chun ; Yen, Chia Jui ; Lai, Hong Yue ; Yuh, Chiou Hwa ; Wu, Wan Chen ; Wang, Ju Ming. / HMDB and 5-AzadC combination reverses tumor suppressor CCAAT/enhancer-binding protein delta to strengthen the death of liver cancer cells. 於: Molecular Cancer Therapeutics. 2015 ; 卷 14, 編號 11. 頁 2623-2633.
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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 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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AU - Yuh, Chiou Hwa

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AU - Wang, Ju Ming

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