Gene expression profiling of KBH-A42, a novel histone deacetylase inhibitor, in human leukemia and bladder cancer cell lines

Kang, Moo Rim; Kang, Jong Soon; Yang, Jeong Wook; Kim, Bo Geun; Kim, Jin Ah; Jo, Yeong Nang; Lee, Kiho; Lee, Chang Woo; Lee, Ki Hoon; Yun, Jieun; Kim, Hwan Mook; Han, Gyoonhee; Kang, Jong Seong; Park, Song Kyu

doi:10.3892/ol.2011.430

Cited by 13 publications

(7 citation statements)

References 19 publications

(18 reference statements)

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“…It was previously reported that TNFRSF10B could be a tumor suppressor gene since it triggered p53-mediated apoptosis in cancer cells (Takimoto and El-Deiry 2000). In addition, another study also reported that treatment of K562 human chronic myeloid cells with an inhibitor of histone deacetylase, KBH-A42, caused TNFRSF10B overexpression and resulted in apoptosis (Kang et al 2012). Our results are in consistent with the literature and revealed that propranolol treatment resulted in considerable increment in the expression levels of TNFRSF10B gene in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 87%

New indication for therapeutic potential of an old well-known drug (propranolol) for multiple myeloma

Kozanoğlu

Yandım

Çinçin

et al. 2012

J Cancer Res Clin Oncol

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Purpose Propranolol, a non-selective b-adrenergic receptor blocker, has been used for the treatment of the patients with hypertension for more than 50 years. There are several in vitro and in vivo evidences that b-adrenergic receptor antagonists inhibit proliferation and angiogenesis and also increase apoptosis in breast, skin, and colon cancers. The aim of this study was to investigate the cytotoxic and apoptotic effects of propranolol and the genes involved in propranololinduced apoptosis in multiple myeloma cells. Methods Time-dependent antiproliferation and apoptotic effects of propranolol were subsequently determined by MTT cell proliferation assay, changes in caspase-3 activity, loss of mitochondrial membrane potential (MMP), and also the localization of phosphatidylserine in the plasma membrane. Changes in expression levels of NF-JB pathway were examined by qRT-PCR array.Results IC50 values of propranolol on U266 cells were calculated as 141, 100, and 75 lM after 24-, 48-, and 72-h propranolol exposure, respectively. There were significant increases in caspase-3 activity, loss of MMP, and increases in apoptotic cell population in response to propranolol in U266 cells in a time-and dose-dependent manner. There were increases in expression levels of BCL10, TRAF family members, interleukins, TLR1-4, TNFRSF10B, NFjB, and the inhibitors of NF-jB genes, and significant decreases in expression levels of Bcl-2 in response to propranolol treatment were observed. Conclusion These results revealed that propranolol has antiproliferative and apoptotic effects on multiple myeloma cells. Being supported with in vivo analyses, propranolol can be a good and economical way to treat multiple myeloma patients.

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Section: Discussionmentioning

confidence: 87%

New indication for therapeutic potential of an old well-known drug (propranolol) for multiple myeloma

Kozanoğlu

Yandım

Çinçin

et al. 2012

J Cancer Res Clin Oncol

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“…TNFRSF8 is known to function in apoptosis by activating the caspase pathway ( 44 ) and protecting the body against auto immunity. It is a conventional biomarker of hematologic malignancies ( 45 ), but its relationship with solid tumors is unclear.…”

Section: Discussionmentioning

confidence: 99%

Molecular genetic study of novel biomarkers for early diagnosis of oral squamous cell carcinoma

Kim¹,

Eun-Hyoung²,

Kim³

et al. 2015

Med Oral

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Objectives: Early detection and treatment of an oral squamous cell carcinoma (OSCC) is critical because of its rapid growth, frequent lymph-node metastasis, and poor prognosis. However, no clinically-valuable methods of early diagnosis exist, and genetic analysis of OSCCs has yielded no biomarkers. Study Design: We investigated the expression of genes associated with inflammation in OSCCs via a quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) analysis of microarray data. Tumor and normal tissues from five patients with an OSCC were used for microarray analysis. Differentially-expressed genes, identified using permutation, local pooled error (LPE), t-tests, and significance analysis of microarrays (SAM), were selected as candidate genetic markers. Results: Two groups corresponding to tissue identity were evident, implying that their differentially-expressed genes represented biological differences between tissues. Fifteen genes were identified using the Student’s paired t-test (p<0.05) and the SAM, with a false discovery rate of less than 0.02. Based on gene expression, these 15 genes can be used to classify an OSCC. A genetic analysis of functional networks and ontologies, validated by using a qRT-PCR analysis of the tissue samples, identified four genes, ADAM15, CDC7, IL12RB2 and TNFRSF8, that demonstrated excellent concordance with the microarray data. Conclusions: Our study demonstrated that four genes (ADAM15, CDC7, IL12RB2 and TNFRSF8) had potential as novel biomarkers for the diagnosis and the treatment of an OSCC. Key words:Biomarker, microarray, quantitative reverse transcription polymerase chain reaction, oral squamous cell carcinoma, gene expression profiling.

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“…HDAC inhibitors could alter expression of genes that are transcription factors, co-activators, co -repressors or epigenetic enzymes resulting in additional and unpredictable downstream changes in gene expression. Many studies now demonstrate that HDAC inhibitors can decrease expression of particular genes [131][132][133][134]. Indeed, we have recently shown that some HDAC inhibitors produce dose-dependent decreases, while others produce dose-dependent increases in the expression of some KDMs [135].…”

Section: Lysine Deacetylase Inhibitorsmentioning

confidence: 98%

Inhibitors of Enzymes Catalyzing Modifications to Histone Lysine Residues: Structure, Function and Activity

et al. 2016

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Gene expression is partly controlled by epigenetic mechanisms including histone-modifying enzymes. Some diseases are caused by changes in gene expression that can be mitigated by inhibiting histone-modifying enzymes. This review covers the enzyme inhibitors targeting histone lysine modifications. We summarize the enzymatic mechanisms of histone lysine acetylation, deacetylation, methylation and demethylation and discuss the biochemical roles of these modifications in gene expression and in disease. We discuss inhibitors of lysine acetylation, deacetylation, methylation and demethylation defining their structure-activity relationships and their potential mechanisms. We show that there are potentially indiscriminant off-target effects on gene expression even with the use of selective epigenetic enzyme inhibitors.

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Gene expression profiling of KBH-A42, a novel histone deacetylase inhibitor, in human leukemia and bladder cancer cell lines

Cited by 13 publications

References 19 publications

New indication for therapeutic potential of an old well-known drug (propranolol) for multiple myeloma

New indication for therapeutic potential of an old well-known drug (propranolol) for multiple myeloma

Molecular genetic study of novel biomarkers for early diagnosis of oral squamous cell carcinoma

Inhibitors of Enzymes Catalyzing Modifications to Histone Lysine Residues: Structure, Function and Activity

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