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, Wen-Lan; Wang, Ju Ming

doi:10.1158/1535-7163.mct-15-0025

Cited by 18 publications

(22 citation statements)

References 46 publications

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“…Currently, to the best of our knowledge, no conclusive study of the expression levels of C/EBPδ in GC cells has been performed. In liver cancer, C/EBPδ acts as a tumor suppressor (20). In the present study, C/EBPδ was downregulated in GC cells, indicating that C/EBPδ acted as a tumor suppressor.…”

Section: Discussionsupporting

confidence: 58%

CCAAT/enhancer-binding protein α decreases the viability of gastric cancer cells

Tomizawa¹,

Shinozaki²,

Motoyoshi³

et al. 2017

Oncology Letters

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Abstract. CCAAT/enhancer-binding protein (C/EBP) α, C/EBPβ and C/EBPδ are involved in inflammation and cell differentiation. In the present study, their roles in human gastric cancer cells were investigated. The human gastric cancer cell lines MKN45 and MKN74 were subjected to the reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to analyze the expression levels of C/EBPα, C/EBPβ and C/EBPδ. The cells were transfected with expression plasmids for either C/EBPα or C/EBPδ, and subjected to a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay and RT-qPCR for analysis of cyclin D1 expression. Expression levels of C/EBPα and C/EBPδ were decreased in MKN45 and MKN74 cells compared with in normal gastric tissue. Expression levels of C/EBPβ were decreased in MKN45 cells and increased in MKN74 cells. Viability of MKN45 cells was decreased by C/EBPα and C/EBPδ. Viability of MKN74 cells was decreased by C/EBPα, but increased by C/EBPδ. Expression levels of cyclin D1 were decreased in association with C/EBPα and C/EBPδ overexpression in MKN45 cells. Expression levels of cyclin D1 were decreased in association with C/EBPα overexpression, but increased in association with C/EBPδ overexpression, in MKN74 cells. The results of the present study indicate that C/EBPα is potentially useful for the treatment of gastric cancer.

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Section: Discussionsupporting

confidence: 58%

CCAAT/enhancer-binding protein α decreases the viability of gastric cancer cells

Tomizawa¹,

Shinozaki²,

Motoyoshi³

et al. 2017

Oncology Letters

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“…As depicted, over-expressing PDGFR-alpha reduces melanoma and endothelial cell number by affecting several molecular functions (such as Cell-growth and proliferation ; Cell Death and Survival , Cell Signaling ) via up- and down- regulation of several interconnected molecules. Namely, CXCL10/IP-10, miRNA-503, CEBPB and CEBPD, two known onco-suppressor genes [50, 51, 53, 54, 52] were found strongly modified in cells over-expressing PDGFR-alpha, along with other molecules such as CXCL8, IL6, SOCS3, all known to have functional connections with CXCL10/IP-10.…”

Section: Discussionmentioning

confidence: 99%

PDGFR-alpha inhibits melanoma growth via CXCL10/IP-10: a multi-omicsapproach

et al. 2016

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Melanoma is the most aggressive skin-cancer, showing high mortality at advanced stages. Platelet Derived Growth Factor Receptor-alpha (PDGFR-alpha) potently inhibits melanoma- and endothelium-proliferation and its expression is significantly reduced in melanoma-biopsies, suggesting that melanoma progression eliminates cells expressing PDGFR-alpha. In the present study transient overexpression of PDGFR-alpha in endothelial (HUVEC) and melanoma (SKMel-28, A375, Preyer) human-cells shows strong anti-proliferative effects, with profound transcriptome and miRNome deregulation. PDGFR-alpha overexpression strongly affects expression of 82 genes in HUVEC (41 up-, 41 down-regulated), and 52 genes in SKMel-28 (43 up-, 9 down-regulated). CXCL10/IP-10 transcript showed up to 20 fold-increase, with similar changes detectable at the protein level. miRNA expression profiling in cells overexpressing PDGFR-alpha identified 14 miRNAs up- and 40 down-regulated, with miR-503 being the most down-regulated (6.4 fold-reduction). miR-503, miR-630 and miR-424 deregulation was confirmed by qRT-PCR. Interestingly, the most upregulated transcript (i.e., CXCL10/IP-10) was a validated miR-503 target and CXCL10/IP-10 neutralization significantly reverted the anti-proliferative action of PDGFR-alpha, and PDGFR-alpha inhibition by Dasatinb totally reverted the CXCL10/IP10 induction, further supporting a functional interplay of these factors. Finally, integration of transcriptomics and miRNomics data highlighted several pathways affected by PDGFR-alpha.This study demonstrates for the first time that PDGFR-alpha strongly inhibits endothelial and melanoma cells proliferation in a CXCL10/IP-10 dependent way, via miR-503 down-regulation.

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“…1A). Our previous studies suggested that CEBPD is responsive to anticancer drugs (26,27). We further assessed whether CDDP affected CEBPD expression in UCUB cells.…”

Section: Significance Of Cebpd Immunoreactivity In Ucubmentioning

confidence: 97%

Inhibition of the EGFR/STAT3/CEBPD Axis Reverses Cisplatin Cross-resistance with Paclitaxel in the Urothelial Carcinoma of the Urinary Bladder

Wang

Chu

et al. 2017

Clinical Cancer Research

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Purpose: Cisplatin (CDDP) is frequently used in combination chemotherapy with paclitaxel for treating urothelial carcinoma of the urinary bladder (UCUB). CDDP cross-resistance has been suggested to develop with paclitaxel, thus hindering successful UCUB treatment. Therefore, elucidating the mechanisms underlying CDDP-induced anticancer drug resistance is imperative and may provide an insight in developing novel therapeutic strategy.Experimental Design: Loss-of-function assays were performed to elucidate the role of the EGFR and STAT3 in CDDP-induced CCAAT/enhancer-binding protein delta (CEBPD) expression in UCUB cells. Reporter and in vivo DNA-binding assays were employed to determine whether CEBPD directly regulates ATP binding cassette subfamily B member 1 (ABCB1) and ATP binding cassette subfamily C member 2 (ABCC2) activation. Finally, a xenograft animal assay was used to examine the abilities of gefitinib and S3I-201 (a STAT3 inhibitor) to reverse CDDP and paclitaxel sensitivity.Results: CEBPD expression was maintained in postoperative chemotherapy patients, and this expression was induced by CDDP even in CDDP-resistant UCUB cells. Upon CDDP treatment, CEBPD activated ABCB1 and ABCC2. Furthermore, the EGFR/STAT3 pathway contributed to CDDP-induced CEBPD expression in UCUB cells. Gefitinib and S3I-201 treatment significantly reduced the expression of CEBPD and enhanced the sensitivity of CDDP-resistant UCUB cells to CDDP and paclitaxel.Conclusions: Our results revealed the risk of CEBPD activation in CDDP-resistant UCUB cells and suggested a therapeutic strategy for patients with UCUB or UCUB resisted to CDDP and paclitaxel by combination with either gefitinib or S3I-201.

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

Cited by 18 publications

References 46 publications

CCAAT/enhancer-binding protein α decreases the viability of gastric cancer cells

CCAAT/enhancer-binding protein α decreases the viability of gastric cancer cells

PDGFR-alpha inhibits melanoma growth via CXCL10/IP-10: a multi-omicsapproach

Inhibition of the EGFR/STAT3/CEBPD Axis Reverses Cisplatin Cross-resistance with Paclitaxel in the Urothelial Carcinoma of the Urinary Bladder

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