Caspase-3 suppresses diethylnitrosamine-induced hepatocyte death, compensatory proliferation and hepatocarcinogenesis through inhibiting p38 activation

Shang, Na; Bank, Thomas; Ding, Xianzhong; Breslin, Peter; Li, Jun; Shi, Baomin; Qiu, Wei

doi:10.1038/s41419-018-0617-7

Cited by 32 publications

(16 citation statements)

References 41 publications

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“…Apoptosis-related genes strictly regulate cell apoptosis (34), in which Caspase is a cascade of cysteine-aspartic acid-specific proteases (35). The cascade pathway of cell apoptosis mediated by its protein family is activated by the action of multiple factors, and finally leads to cell apoptosis through a series of cascade reactions (36). Caspase-9 is the initiator of the Caspase cascade reaction.…”

Section: Discussionmentioning

confidence: 99%

miR-155 Regulates the Proliferation of Glioma Cells Through PI3K/AKT Signaling

Wang

2020

Front. Neurol.

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Objective: Micro-RNA plays a critical role in the pathological process of gliomas. Previous research showed that the level of miR-155 was significantly increased in many cancers, including gliomas. However, the mechanism of glioma is still unknown. Method: To investigate the regulatory function of miR-155 on glioma U87-MG cells and its effects on related signaling pathways. After transfection of miR-155 mimic and inhibitor, the level of miR-155 were applied to detect cell proliferation, apoptosis, senescence index, invasive ability and cell migration at different time points (0, 24, 24 h, respectively) by CCK8 assay, flow cytometry, β-galactosidase (β-gal) staining, transwell and scratch test, respectively. The effect of miR-155 on PI3K/AKT signal pathway was observed at meantime. Results: Compared with the control group, after miR-155 mimic transfection, U87-MG cell viability, cell migration rate and invasiveness were increased, while apoptosis and senescence were significantly decreased, which was the opposite on miR-155 inhibitor transfection. The phosphorylation levels of miR-155, PI3K, AKT, PI3K, and AKT in U87-MG cells intervened with miR-155 mimic also increased significantly, while the levels of PTEN, Caspase-3, Caspase-9 mRNA, and protein declined significantly, with statistically significant difference. Meanwhile, compared with the control group, miR-155 inhibitor group were on the contrary. Conclusion: The study indicated that miR-155 take charge a key function in regulating the proliferation, migration, and invasion of glioma U87-MG cells through PI3K/AKT signaling pathway, and has anti-glioma effects by inhibition of miR-155, which provided ideas for further clinical treatment of glioma patients.

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Section: Discussionmentioning

confidence: 99%

miR-155 Regulates the Proliferation of Glioma Cells Through PI3K/AKT Signaling

Wang

2020

Front. Neurol.

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“…IL-6 is highly upregulated in PLC, which is correlated with rapid progression from hepatitis to PLC [47]. Previous studies found that CASP3 (Caspase-3) can prevent chemical-induced PLC by suppressing p38 activation and hepatocyte death [48], and total flavonoids from Ampelopsis grossedentata (Teng cha) exerts an antitumor effect on PLC by upregulating the [49]. It is reported that PLC patients with high phosphorylated MAPK3 (also called ERK1) had significantly higher cancer recurrence and worse OS [50], and the impact of MAPK3 on survival was also verified by the survival curve in this study.…”

Section: Discussionmentioning

confidence: 99%

Systematic Elucidation of the Potential Mechanisms of Core Chinese Materia Medicas in Treating Liver Cancer Based on Network Pharmacology

Yang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Objective. In this study, the data mining method was used to screen the core Chinese materia medicas (CCMMs) against primary liver cancer (PLC), and the potential mechanisms of CCMMs in treating PLC were analyzed based on network pharmacology. Methods. Traditional Chinese medicine (TCM) prescriptions for treating PLC were obtained from a famous TCM doctor in Shenzhen, China. According to the data mining technique, the TCM Inheritance Support System (TCMISS) was applied to excavate the CCMMs in the prescriptions. Then, bioactive ingredients and corresponding targets of CCMMs were collected using three different TCM online databases, and target genes of PLC were obtained from GeneCards and OMIM. Afterwards, common targets of CCMMs and PLC were screened. Furthermore, a network of CCMMs bioactive ingredients and common target gene was constructed by Cytoscape 3.7.1, and gene ontology (GO) and signaling pathways analyses were performed to explain the mechanism of CCMMs in treating PLC. Besides, protein-protein interaction (PPI) analysis was used to identify key target genes of CCMMs, and the prognostic value of key target genes was verified using survival analysis. Results. A total of 15 high-frequency Chinese materia medica combinations were found, and CCMMs (including Paeoniae Radix Alba, Radix Bupleuri, Macrocephalae Rhizoma, Coicis Semen, Poria, and Curcumae Radix) were identified by TCMISS. A total of 40 bioactive ingredients (e.g., quercetin, kaempferol, and naringenin) of CCMMs were obtained, and 202 common target genes of CCMMs and PLC were screened. GO analysis indicated that biological processes of CCMMs were mainly involved in response to drug, response to ethanol, etc. Pathway analysis demonstrated that CCMMs exerted its antitumor effects by acting on multiple signaling pathways, including PI3K-Akt, TNF, and MAPK pathways. Also, some key target genes of CCMMs were determined by PPI analysis, and four genes (MAPK3, VEGFA, EGF, and EGFR) were found to be correlated with survival in PLC patients. Conclusion. Based on data mining and network pharmacology methods, our results showed that the therapeutic effect of CCMMs on PLC may be realized by acting on multitargets and multipathways related to the occurrence and development of PLC.

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“…It is directly or indirectly responsible for the cleavage of many proteins and caspases involved in apoptosis. 25 It is activated when cleaved into two protein fragments. Cleaved caspase-3 is responsible for the proteolytic cleavage of many critical proteins.…”

Section: Introductionmentioning

confidence: 99%

Restriction of H1N1 influenza virus infection by selenium nanoparticles loaded with ribavirin via resisting caspase-3 apoptotic pathway

Lin¹,

Li²,

Gong³

et al. 2018

IJN

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IntroductionRibavirin (RBV) is a broad-spectrum antiviral drug. Selenium nanoparticles (SeNPs) attract much attention in the biomedical field and are used as carriers of drugs in current research studies. In this study, SeNPs were decorated by RBV, and the novel nanoparticle system was well characterized. Madin-Darby Canine Kidney cells were infected with H1N1 influenza virus before treatment with RBV, SeNPs, and SeNPs loaded with RBV (Se@RBV).Methods and resultsMTT assay showed that Se@RBV nanoparticles protect cells during H1N1 infection in vitro. Se@RBV depressed virus titer in the culture supernatant. Intracellular localization detection revealed that Se@RBV accumulated in lysosome and escaped to cytoplasm as time elapsed. Furthermore, activation of caspase-3 was resisted by Se@RBV. Expressions of proteins related to caspase-3, including cleaved poly-ADP-ribose polymerase, caspase-8, and Bax, were downregulated evidently after treatment with Se@RBV compared with the untreated infection group. In addition, phosphorylations of phosphorylated 38 (p38), JNK, and phosphorylated 53 (p53) were inhibited as well. In vivo experiments indicated that Se@RBV was found to prevent lung injury in H1N1-infected mice through hematoxylin and eosin staining. Tunel test of lung tissues present that DNA damage reached a high level but reduced substantially when treated with Se@RBV. Immunohistochemical test revealed an identical result with the in vitro experiment that activations of caspase-3 and proteins on the apoptosis pathway were restrained by Se@RBV treatment.ConclusionTaken together, this study elaborates that Se@RBV is a novel promising agent against H1N1 influenza virus infection.

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Caspase-3 suppresses diethylnitrosamine-induced hepatocyte death, compensatory proliferation and hepatocarcinogenesis through inhibiting p38 activation

Cited by 32 publications

References 41 publications

miR-155 Regulates the Proliferation of Glioma Cells Through PI3K/AKT Signaling

miR-155 Regulates the Proliferation of Glioma Cells Through PI3K/AKT Signaling

Systematic Elucidation of the Potential Mechanisms of Core Chinese Materia Medicas in Treating Liver Cancer Based on Network Pharmacology

Restriction of H1N1 influenza virus infection by selenium nanoparticles loaded with ribavirin via resisting caspase-3 apoptotic pathway

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