PP-10 induces apoptosis via JNK/SPAK activation and STAT3 inhibition in Hepatocarcinoma cells in vitro

Soluble epoxide hydrolase (sEH) metabolizes epoxyeicosatrienoic acids (EETs), primarily 14,15-EET. EETs are derived from arachidonic acid via P-450 epoxygenases and are cardioprotective. We tested the hypothesis that sEH deficiency and pharmacological inhibition elicit tolerance to ischemia via EET-mediated STAT3 signaling in vitro and in vivo. In addition, the relevance of single nucleotide polymorphisms (SNPs) of EPHX2 (the gene encoding sEH) on tolerance to oxygen and glucose deprivation and reoxygenation and glucose repletion (OGD/RGR) was assessed in male C57BL\6J (WT) or sEH knockout (sEHKO) cardiomyocytes by using transactivator of transcription (TAT)-mediated transduction with sEH mutant proteins. Cell death and hydrolase activity was lower in Arg287Gln EPHX2 mutants vs. nontransduced controls. Excess 14,15-EET and SEH inhibition did not improve cell survival in Arg287Gln mutants. In WT cells, the putative EET receptor antagonist, 14,15-EEZE, abolished the effect of 14,15-EET and sEH inhibition. Cotreatment with 14,15-EET and SEH inhibition did not provide increased protection. In vitro, STAT3 inhibition blocked 14,15-EET cytoprotection, but not the effect of SEH inhibition. However, STAT3 small interfering RNA (siRNA) abolished cytoprotection by 14,15-EET and sEH inhibition, but cells pretreated with JAK2 siRNA remained protected. In vivo, STAT3 inhibition abolished 14,15-EET-mediated infarct size reduction. In summary, the Arg287Gln mutation is associated with improved tolerance against ischemia in vitro, and inhibition of sEH preserves cardiomyocyte viability following OGD/RGR via an EET-dependent mechanism. In vivo and in vitro, 14,15-EET-mediated protection is mediated in part by STAT3.

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Modified Yi Guan Jian, a Chinese herbal formula, induces anoikis in Bel-7402 human hepatocarcinoma cells in vitro

Oncology Reports ◽

10.3892/or.2011.1414 ◽

2011 ◽

Cited By ~ 6

Author(s):

Bing Hu

Keyword(s):

Herbal Formula ◽

Chinese Herbal Formula ◽

Chinese Herbal ◽

Hepatocarcinoma Cells ◽

Human Hepatocarcinoma Cells

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Transcriptional gene expression profile in hepatocarcinoma cells induced by acetylsalicylic acid (ASA) in hepatitis C virus (HCV)-subgenomic replicon system.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e22016 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e22016-e22016

Author(s):

Clara Patricia Rios Ibarra ◽

Barbara Verduzco Garza ◽

Rocio Ortiz Lopez ◽

Yohann Grondin ◽

Sonia Lozano Sepulveda ◽

...

Keyword(s):

Gene Expression ◽

Signaling Pathway ◽

Expression Profile ◽

Molecular Mechanisms ◽

Antiviral Effect ◽

Subgenomic Replicon ◽

Expression Of Genes ◽

Antioxidant Agents ◽

Hepatocarcinoma Cells

e22016 Background: It has been demonstrated that ASA treatment could down-regulate in vitro HCV expression in hepatocarcinoma cells (~50%, p 0.05). However, the signaling pathway induced during ASA antiviral effect has not been elucidated. We analyzed the transcriptional expression profile of Huh-7-HCV-subgenomic replicon cells in presence or absence of ASA in order to identify the signaling pathway and the molecular mechanisms involved in the antiviral effect induced by ASA on HCV expression. Methods: Huh-7-HCV-replicon cells (hepatocarcinoma) were exposed to 4 mM ASA from 24 to 72 hours. Total RNA was isolated, quantified and validated by capillary electrophoresis. After that, we performed a retrotranscription in vitro. Synthesized transcripts were marked with biotin, purified, fragmentized and hybridized in HG-U133 Plus 2 Gene Expression. Hybridization signals were captured with Gen Chip 3000 7G Scanner and analyzed by Expression Console and Dchit Software. Results: After normalization, we obtained hierarchical maps with differentially-expressed genes. Among genetic targets over-expressed, the following stood out CCAAT-enhancer-binding proteins (C/EBP), interleukine-8 (IL-8), cytochrome P450 (CyP450) and methallothioneins (MT) genes were found. Among down-regulated genes we identified ribonucleotide reductase (RR) and superoxide dismutase (SOD) genes. Some of these genes have been previously associated with oxidative stress regulation. All results were validated by real time PCR. Conclusions: We observed that ASA modulates the expression of genes associated with antioxidant role as SOD and methallothioneins. Antioxidant agents can inhibit virus proliferation. HCV decreased antioxidant defense, which promotes the development of hepatic complications caused by HCV infection, including liver cancer. Therefore, ASA could be inducing an antioxidant environment regulating HCV replication. This study provides a tool for identifying novel host factors in hepatocarcinoma cells involved in the antiviral effect regulated by ASA against HCV and improves our understanding of the regulatory mechanism of HCV replication.

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Abstract 3195: STAT3 inhibition using shRNA inhibits GBM proliferation, cell migration, anchorage-independent growth of mouse, rat, and human stem-like cells in vitro; and it induces long term survival and anti-GBM immunity in vivo

10.1158/1538-7445.am2015-3195 ◽

2015 ◽

Author(s):

Nathan T. VanderVeen ◽

Nicholas Raja ◽

Elizabeth Yi ◽

James Curtin ◽

Peter Chockley ◽

...

Keyword(s):

Cell Migration ◽

Term Survival ◽

Long Term Survival ◽

Anchorage Independent Growth ◽

Stat3 Inhibition

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Studies on the Inhibitory Effects of Nano-Hydroxyapatite-Loaded As2O3 on Hepatoma Cells

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2020.18715 ◽

2020 ◽

Vol 20 (12) ◽

pp. 7451-7456

Author(s):

Jun Xue ◽

Yanke Hu ◽

Yinxia Su ◽

Tangmeng Guo ◽

Yunqiao Li

Keyword(s):

Cell Cycle ◽

Colorimetric Assay ◽

Ultrasound Irradiation ◽

Inhibitory Effect ◽

Cell Swelling ◽

Morphological Observation ◽

Nanoparticle Suspension ◽

Hepatocarcinoma Cells ◽

Human Hepatocarcinoma Cells

A stable monodisperse hydroxyapatite (HAP) nanoparticle suspension was prepared by chemical method-assisted ultrasound irradiation. HAP nanoparticles were characterized by atomic force microscopy (AFM) and particle size potentiometry. The effects of HAP nanoparticles on BEL-7402 human hepatocarcinoma cells were studied by MTT colorimetric assay and morphological observation. The mechanism of HAP nanoparticles was studied by analyzing single cell fluorescence element microregion, the change of ultrastructure and cell cycle. The experimental results show that HAP nanoparticles have an obvious inhibitory effect on BEL-7402 human hepatocarcinoma cells in vitro. By entering the cancer cells and blocking the progress of cell cycle, HAP nanoparticles induce the accumulation of cells in G1 phase, which leads to cancer cell swelling and apoptosis.

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The Natural-Based Antitumor Compound T21 Decreases Survivin Levels through Potent STAT3 Inhibition in Lung Cancer Models

Biomolecules ◽

10.3390/biom9080361 ◽

2019 ◽

Vol 9 (8) ◽

pp. 361 ◽

Cited By ~ 7

Author(s):

David Martínez-García ◽

Marta Pérez-Hernández ◽

Luís Korrodi-Gregório ◽

Roberto Quesada ◽

Ricard Ramos ◽

...

Keyword(s):

Lung Cancer ◽

Marine Invertebrates ◽

Antitumor Agent ◽

Janus Kinase ◽

Therapeutic Drug ◽

Novel Treatments ◽

Cancer Models ◽

Stat3 Inhibition ◽

Anticancer Compound

Lung cancer is the leading cause of cancer-related deaths worldwide; hence novel treatments for this malignancy are eagerly needed. Since natural-based compounds represent a rich source of novel chemical entities in drug discovery, we have focused our attention on tambjamines, natural compounds isolated from marine invertebrates that have shown diverse pharmacological activities. Based on these structures, we have recently identified the novel indole-based tambjamine analog 21 (T21) as a promising antitumor agent, which modulates the expression of apoptotic proteins such as survivin. This antiapoptotic protein plays an important role in carcinogenesis and chemoresistance. In this work, we have elucidated the molecular mechanism by which the anticancer compound T21 exerts survivin inhibition and have validated this protein as a therapeutic target in different lung cancer models. T21 was able to reduce survivin protein levels in vitro by repressing its gene expression through the blockade of Janus kinase/Signal Transducer and Activator of Transcription-3 (JAK/STAT3)/survivin signaling pathway. Interestingly, this occurred even when the pathway was overstimulated with its ligand interleukin 6 (IL-6), which is frequently overexpressed in lung cancer patients who show poor clinical outcomes. Altogether, these results show T21 as a potent anticancer compound that effectively decreases survivin levels through STAT3 inhibition in lung cancer, appearing as a promising therapeutic drug for cancer treatment.

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GdCl3 reduces hyperglycaemia through Akt/FoxO1-induced suppression of hepatic gluconeogenesis in Type 2 diabetic mice

Clinical Science ◽

10.1042/cs20130670 ◽

2014 ◽

Vol 127 (2) ◽

pp. 91-100 ◽

Cited By ~ 15

Author(s):

Qian Wang ◽

Ning Wang ◽

Mei Dong ◽

Fang Chen ◽

Zhong Li ◽

...

Keyword(s):

Therapeutic Target ◽

Diabetic Mice ◽

Hepatic Gluconeogenesis ◽

Potential Therapeutic Target ◽

Hepatocarcinoma Cells ◽

Type 2 Diabetic

In the present study, we demonstrate that GdCl3 reduces hyperglycaemia via the Akt/FoxO1-induced suppression of hepatic gluconeogenesis, both in Type 2 diabetic mice (in vivo) and in hepatocarcinoma cells (in vitro), suggesting that GdCl3 may be a potential therapeutic target for diabetes.

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