Growth inhibition of human hepatocellular carcinoma cells by antagonism of the β2 adrenergic receptor

Dang, Dongmei; Zhang, Jing; Yang, Jianjun

doi:10.3892/ol.2018.8847

Cited by 2 publications

(2 citation statements)

References 23 publications

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“…Another gene found to be strongly upregulated by entolimod in our study is RCAN1 (regulator of calcineurin 1), which was previously shown to preserve endothelial integrity and reduce vascular barrier breakdown by increasing resistance to damaging systemic anaphylaxis [52]. Anti-apoptotic factors strongly induced by entolimod that may contribute to entolimod's tissue protective activity in the liver include early stress response genes of the IER-3 and BCL2 families [53] and the adrenergic receptor ADRB2 [54].…”

Section: Pro-survival Transcriptional Response To Entolimod In the Mumentioning

confidence: 56%

TLR5 agonist entolimod reduces the adverse toxicity of TNF while preserving its antitumor effects

et al. 2020

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Tumor necrosis factor alpha (TNF) is capable of inducing regression of solid tumors. However, TNF released in response to Toll-like receptor 4 (TLR4) activation by bacterial lipopolysaccharide (LPS) is the key mediator of cytokine storm and septic shock that can cause severe tissue damage limiting anticancer applications of this cytokine. In our previous studies, we demonstrated that activation of another Toll-like receptor, TLR5, could protect from tissue damage caused by a variety of stresses including radiation, chemotherapy, Fas-activating antibody and ischemia-reperfusion. In this study, we tested whether entolimod could counteract TNF-induced toxicity in mouse models. We found that entolimod pretreatment effectively protects livers and lungs from LPS-and TNF-induced toxicity and prevents mortality caused by combining either of these agents with the sensitizer, D-galactosamine. While LPS and TNF induced significant activation of apoptotic caspase 3/7, lipid tissue peroxidation and serum ALT accumulation in mice without entolimod treatment, these indicators of toxicity were reduced by entolimod pretreatment to the levels of untreated control mice. Entolimod was effective when injected 0.5-48 hours prior to, but not when injected simultaneously or after LPS or TNF. Using chimeric mice with hematopoiesis differing in its TLR5 status from the rest of tissues, we showed that this protective activity was dependent on TLR5 expression by non-hematopoietic cells. Gene expression analysis identified multiple genes upregulated by entolimod in the liver and cultured hepatocytes as possible mediators of its protective activity. Entolimod did not interfere with the antitumor activity of TNF in mouse hepatocellular and colorectal tumor models. These results support further development of TLR5 agonists to increase tissue resistance to cytotoxic cytokines, reduce the risk of septic shock and enable safe systemic application of TNF as an anticancer therapy.

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Section: Pro-survival Transcriptional Response To Entolimod In the Mumentioning

confidence: 56%

TLR5 agonist entolimod reduces the adverse toxicity of TNF while preserving its antitumor effects

et al. 2020

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“…It is reported that activation of ADRB2 promotes EMS development by stress and surgery [28–30]. In cancer and cardiomyocytes, ADRB2 inhibits apoptosis mainly through Bcl-2/Bax/caspase-9 pathway [31–35]. Herein, ADRB2 might be the therapeutic target in EMS.…”

Section: Discussionmentioning

confidence: 99%

Jiawei Foshou San Induces Apoptosis in Ectopic Endometrium Based on Systems Pharmacology, Molecular Docking, and Experimental Evidence

Jiang

Zhao

Zhang

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Foshou San is a typical gynaecological formula with wild usage in traditional Chinese medicine. Jiawei Foshou San (JFS) is a novel ingredient prescription from Foshou San with antiendometriosis effect in unclear mechanisms. To uncover the potential application and proapoptotic mechanisms of JFS, JFS ingredient-drug target-disease networks, GO enrichment, and pathway analysis were established for potential application prediction. Molecular docking and validation in vivo were investigated by the proapoptotic mechanisms of JFS. In this study, 99 common targets were related to 108 diseases. 484 biological processes, 44 cell components, 59 molecular functions, and 37 pathways were significantly identified in GO enrichment and pathway analysis. In molecular docking, ligustrazine showed binding activity with Bcl-2, Bax, caspase-9, caspase-3, and PARP. In vivo, JFS elevated the shrink rate of ectopic endometrium, by suppressing E2 and PROG. An in-depth study showed that apoptosis was activated through diminishing Bcl-2, rising Bax and Bad, and expressing more caspase-3 and caspase-9 using JFS. JFS promoted the protein level of cleaved-PARP. In brief, JFS might be applied for various diseases through multiple targets and pathways, especially endometriosis by Bcl-2 pathway. These findings reveal the potential application for further evaluation and uncover the proapoptotic mechanism of JFS.

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Growth inhibition of human hepatocellular carcinoma cells by antagonism of the β2 adrenergic receptor

Cited by 2 publications

References 23 publications

TLR5 agonist entolimod reduces the adverse toxicity of TNF while preserving its antitumor effects

TLR5 agonist entolimod reduces the adverse toxicity of TNF while preserving its antitumor effects

Jiawei Foshou San Induces Apoptosis in Ectopic Endometrium Based on Systems Pharmacology, Molecular Docking, and Experimental Evidence

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