Tanshinone I induces cell apoptosis by reactive oxygen species-mediated endoplasmic reticulum stress and by suppressing p53/DRAM-mediated autophagy in human hepatocellular carcinoma

Liu, Xu; Liu, Ji‑kui

doi:10.1080/21691401.2019.1709862

Cited by 31 publications

(20 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When dysfunction occurs in the ER, all cells are programmed to respond to it. However, when the ER stress process is prolonged and intensi ed, the proapoptotic process becomes dominant and ER stress can cause cell apoptosis [17]. The role of ER stress, an important mechanism mediating apoptosis, has not been investigated in the etiopathogenesis of chronic tonsillitis and tonsillar hypertrophy.…”

Section: Discussionmentioning

confidence: 99%

Relationship of endoplasmic reticulum stress with the etiopathogenesis of chronic tonsillitis and tonsillar hypertrophy in pediatric patients: a prospective, parallel-group study

et al. 2021

View full text Add to dashboard Cite

Objectives: Tonsil tissue is a very important component of the human immunity system, contributing to the functioning of the cellular and humoral defence system, especially in childhood. The endoplasmic reticulum (ER) is an organelle that has a very important function in the balanced functioning of cells, in which the accumulation of a cellular protein called ER stress occurs in case of dysfunction. ER stress in uences the pathogenesis of many diseases and immune system functions. We aimed to investigate the relation between the diseases of tonsil tissue and ER stress response to elucidate the mechanisms of diseases related with the immune system.Methods: A prospective study was conducted in 46 children aged between 2 and 16 years who underwent tonsillectomy for chronic tonsillitis or tonsillar hypertrophy. Tonsil tissue was separated into two groups according to their size and evaluated in terms of ER stress markers and apoptosis markers by Real-time PCR and Western blot analysis.Results: The ΔCT levels of ER stress markers (ATF4, ATF6, CHOP, GRP78, EIF2AK3, ERN1, GRP94) were greater in children with chronic tonsillitis (p < 0.005). In contrast, the tonsillar hypertrophy group had greater ΔCT levels of apoptosis markers (BAX, BCL-2) according to the Real-time PCR method (p < 0.005). According to the Western blot analysis, the normalized levels of ATF4, ATF6, CHOP, GRP78, and ERN1 genes were found greater in the chronic tonsillitis group than the tonsillar hypertrophy group. There was no difference between the two groups in terms of normalized BCL-2 and BAX levels by Western blot analysis.Conclusion: This is the rst study in the literature investigating the effect of the ER stress pathway on the etiopathogenesis of tonsil diseases. It was concluded that the ER stress pathway plays a role in the etiopathogenesis of chronic tonsillitis. Investigating the relationship between ER stress and structures such as the tonsil tissue that make up the immune system can help create new treatment strategies.Trial Registration ClinicalTrials.gov Identi er: NCT04653376

show abstract

Section: Discussionmentioning

confidence: 99%

Relationship of endoplasmic reticulum stress with the etiopathogenesis of chronic tonsillitis and tonsillar hypertrophy in pediatric patients: a prospective, parallel-group study

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The response of these biological functions on steroid hormones coincided with the target AR and ESR1, suggesting that SNS may regulate the levels of sex hormones. Histone H3 phosphorylation is involved in the chemical carcinogenesis of HCC, while histone 4 phosphorylation is related to the proliferation and differentiation of hepatocytes after a liver injury ( Sukumar et al, 2020 ; Liu & Liu, 2020 ). The potential pathways are: the p53 signaling pathway; calcium signaling pathway; NF-kappa B signaling pathway; and the HIF-1 signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Determining novel candidate anti-hepatocellular carcinoma drugs using interaction networks and molecular docking between drug targets and natural compounds of SiNiSan

Zhang

Feng

Gao

et al. 2021

PeerJ

View full text Add to dashboard Cite

Background SiNiSan (SNS) is an ancient traditional Chinese medicine (TCM) used to treat liver and spleen deficiencies. We studied the unique advantages of using SNS to treat hepatocellular carcinoma (HCC) with multiple components and targets to determine its potential mechanism of action. Methods The active compounds from the individual herbs in the SNS formula and their targets were mined from Traditional Chinese Medicine Systems Pharmacology Database (TCMSP). HCC-associated targets were collected from the TCGA and GEO databases and samples were collected from patients with stage III hepatocellular carcinoma. A compound-disease target network was constructed, visualized, and analyzed using Cytoscape software. We built a protein-protein interaction (PPI) network using the String database. We enriched and analyzed key targets using GSEA, GO, and KEGG in order to explore their functions. Autodock software was used to simulate the process of SNS molecules acting on HCC targets. Results A total of 113 candidate compounds were taken from SNS, and 64 of the same targets were chosen from HCC and SNS. The predominant targets genes were PTGS2, ESR1, CHEK1, CCNA2, NOS2 and AR; kaempferol and quercetin from SNS were the principal ingredients in HCC treatment. The compounds may work against HCC due to a cellular response to steroid hormones and histone phosphorylation. The P53 signaling pathway was significantly enriched in the gene set GSEA enrichment analysis and differential gene KEGG enrichment analysis. Conclusions Our results showed that the SNS component has a large number of stage III HCC targets. Among the targets, the sex hormone receptors, the AR and ESR1 genes, are the core targets of SNS component and the most active proteins in the PPI network. In addition, quercetin, which has the most targets, can act on the main targets (BAX, CDK1, CCNB1, SERPINE1, CHEK2, and IGFBP3) of the P53 pathway to treat HCC.

show abstract

“…Damage-regulated autophagy modulator (DRAM) is a lysosomal protein involved in P53-rugulated autophagy induction [25,26]. Studies have found that DRAM leads to increased expression of beclin1 and production of p53 [27].…”

Section: Discussionmentioning

confidence: 99%

P53/DRAM/ autophagy - a new target for improving the therapeutic effect of anti-VEGF on intraocular neovascularization

Wang

Yao²,

et al. 2020

Preprint

View full text Add to dashboard Cite

Backgroud Recurrence of intraocular neovascularization is a major clinical problem. Anti-VEGF drugs are the main treatment for intraocular neovascularization currently. However, anti-VEGF drugs can activate endothelial autophagy and weaken the therapeutic effect. This study aims to elucidate the effect and mechanism of anti-VEGF drugs on autophagy of vascular endothelial cells. Methods RF/6A cells were randomly divided into five groups: The control group, hypoxia group (1% O2、5% CO2、94% N2), anti-VEGF group(group1:Ranibizumab 100ug/ml; group2: Aflibercept, 400ug/ml; group3: Conbercept, 100ug/ml) and autophagy inhibition group(3-MA or CQ) which was corresponding to anti-VEGF group. Autophagy-related proteins were examined by Western blot. RFP-GFP-LC3 was used to detect autophagy and autophagic flow. CCK-8 assay was used to detect cell proliferation. Flow cytometry and Tunel was used to detect cell apoptosis. Cell migration and tube formation were assessed by wound assay and matrix method, respectively. Results Ranibizumab and Conbercept can triger autophagy in hypoxia condition in RF/6A cells, while Aflibercept can inhibit autophagy. Conbercept combined with autophagy inhibitor (3-MA or CQ) could inhibit cell migration and tube formation of RF/6A cells more effectively in hypoxia condition. For mechanism, p53 and DRAM proteins paly an important role in Conbercept induced autophagy. Inhibition of P53 can suppressed the autophagy induced by Conbercept. Conclusion Ranibizumab and Conbercept can triger the autophagy of vascular endothelial cells while Aflibercept can inhibit it. The combination of ranibizumab/ Concept and autophagy inhibitor can significantly inhibit the formation of angiogenesis in vitro. The mechanism of autophagy activation is related to the activation of p53 / DRAM pathway.

show abstract

Tanshinone I induces cell apoptosis by reactive oxygen species-mediated endoplasmic reticulum stress and by suppressing p53/DRAM-mediated autophagy in human hepatocellular carcinoma

Abstract: (2020) Tanshinone I induces cell apoptosis by reactive oxygen species-mediated endoplasmic reticulum stress and by suppressing p53/DRAM-mediated autophagy in human hepatocellular carcinoma,

Cited by 31 publications

References 37 publications

Relationship of endoplasmic reticulum stress with the etiopathogenesis of chronic tonsillitis and tonsillar hypertrophy in pediatric patients: a prospective, parallel-group study

Relationship of endoplasmic reticulum stress with the etiopathogenesis of chronic tonsillitis and tonsillar hypertrophy in pediatric patients: a prospective, parallel-group study

Determining novel candidate anti-hepatocellular carcinoma drugs using interaction networks and molecular docking between drug targets and natural compounds of SiNiSan

P53/DRAM/ autophagy - a new target for improving the therapeutic effect of anti-VEGF on intraocular neovascularization

Contact Info

Product

Resources

About