Celastrol suppresses expression of adhesion molecules and chemokines by inhibiting JNK-STAT1/NF-κB activation in poly(I:C)-stimulated astrocytes

An, Soo Yeon; Youn, Gi Soo; Kim, Hye-Jin; Choi, Soo Young; Park, Jinseu

doi:10.5483/bmbrep.2017.50.1.114

Cited by 23 publications

(10 citation statements)

References 26 publications

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“…Zhang J claimed that celastrol ameliortes inflammation on Human Retinal Pigment Epithelial Cells . An SY demonstrated that celastrol can significantly suppress microbial processes . According to the recent discovery, celastrol exhibits an antitumor effect on several cancer cells through inhibiting cell survival, invasion/migration, and angiogenesis or promoting cell apoptosis in a wide variety of tumor models, including osteosarcoma, colorectal cancer, liver cancer, lung cancer, and breast cancer .…”

Section: Introductionmentioning

confidence: 99%

Antitumor activity of celastrol by inhibition of proliferation, invasion, and migration in cholangiocarcinoma via PTEN/PI3K/Akt pathway

Zhu

Wei

2019

Cancer Medicine

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Aim: Cholangiocarcinoma is a malignant tumor originating from bile duct epithelium. Currently, the treatment strategy is very limited and the prognosis is poor.Recent studies reported celastrol exhibits antigrowth and antimetastasis properties in many tumors. Our study aimed to assess the anti-CCA effects of cholangiocarcinoma (CCA) and the mechanisms involved in it. Methods: In this study, the long-term and short-term antiproliferation effects was determined using colony formation and Cell Counting Kit-8 (CCK-8) assays, respectively. Flow cytometry was performed to quantify apoptosis. Furthermore, wound healing and transwell assays were performed to determine the cell migration and invasion capabilities, respectively. To further find the mechanism involved in the celastrol-induced biological functions, LY204002, a PI3K/Akt signaling inhibitor, and an Akt-1 overexpression plasmid were employed to find whether PI3K/Akt pathway was involved in the celastrol-induced CCA cell inhibition. Additionally, short interfering RNA (siRNA) was also used to investigate the mechanism involved in the celastrol-induced PI3K/Akt signaling inhibition. Western blotting and immunofluorescence assays were also performed to detect the degree of relative proteins.Moreover, we validated the antiproliferation and antimetastasis effects of celastrol in vivo by constructing subcutaneous and lung metastasis nude mice models. Results: We discovered that celastrol effectively induced apoptotic cell death and inhibited the capacity of migration and invasion in CCA cells. Further mechanistic study identified that celastrol regulated the PI3K/Akt signaling pathway, and the antitumor efficacy was likely due to the upregulation of PTEN, a negative regulator of PI3K/Akt. Blockage of PTEN abolished the celastrol-induced PI3K/Akt signaling inhibition. Additionally, in vivo experiments conformed celastrol inhibited the tumor growth and lung metastasis with no serious side effects. Conclusions: Overall, our study elucidated a mechanistic framework for the anti-CCA effects of celastrol via PTEN/PI3K/Akt pathway. 784 | ZHU and WEI K E Y W O R D S Akt, apoptosis, celastrol, epithelial-to-mesenchymal transition, phosphatase and tensin homolog

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Section: Introductionmentioning

confidence: 99%

Antitumor activity of celastrol by inhibition of proliferation, invasion, and migration in cholangiocarcinoma via PTEN/PI3K/Akt pathway

Zhu

Wei

2019

Cancer Medicine

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“…Inhibitors of p38, JNK, and NF-jB pathways suppressed CCL2 induction by IL-1b and TNFa in primary rat astrocytes (Thompson and van Eldik 2009). The inhibition of JNK phosphorylation reduced CCL2 expression induced by interferon (IFN)-c and poly(I:C) (polyinosinic-polycyti-dylic acid) in primary rat astrocytes and CRT-MG human astroglioma cells (Lee et al 2008(Lee et al , 2012An et al 2017). It was earlier shown that Cd (as CdCl 2 ) at 1 and 10 lM increased phosphorylation of ERK1/2, p38 MAPK, and p65 NF-jB after 30 min (Phuagkhaopong et al 2017).…”

Section: Discussionmentioning

confidence: 98%

Cadmium induces CCL2 production in glioblastoma cells via activation of MAPK, PI3K, and PKC pathways

Kasemsuk

Phuagkhaopong

Yubolphan

et al. 2020

Journal of Immunotoxicology

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Cadmium (Cd) is accumulated in human astrocytes and induces the production of interleukin (IL)-6 and IL-8. Astrocytes are one of the major sources of chemokine CC motif ligand 2 (CCL2; known as monocyte chemoattractant protein-1 [MCP-1]), in the brain. Elevated CCL2 levels are associated with cognitive impairment as well as the migration and invasion of glioblastoma cells. The present study hypothesized that non-toxic concentrations of Cd (as cadmium chloride [CdCl 2 ]) could up-regulate CCL2 production in U-87 MG human glio-blastoma cells. The results showed that after exposure of the U-87 MG cells to CdCl 2 at 1 and 10 mM, there was an up-regulation of CCL2 mRNA expression after 3 h of exposure and increased CCL2 secretion after 6 and 24 h. The study also found that inhibition of MAPK pathways, including ERK1/ 2, p38, and JNK by U0126, SB203580 and SP600125, respectively, reduced Cd-induced CCL2 secretion by the cells. Moreover, when cells were pretreated with Ro 32-0432 (an inhibitor of calcium-dependent PKC) and LY294002 (a PI3K inhibitor), this also resulted in a down-regulation of any Cd-induced CCL2 expression. Taken together, the results of this study allow for the conclusion to be made that CCL2 up-regulation in U-87 MG cells induced by Cd is mediated, in part, by an activation of MAPK, PI3K/Akt, and PKC pathways.

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“…Intracellular ROS levels were detected using fluorescence microscopy with DCFH-DA (Beyotime Biotechnology, Beijing, China). The DCFH-DA was intracellularly deacetylated by a nonspecific esterase, further oxidized by ROS to produce the fluorescent compound 2,7-dichlorofluorescein (DCF) ( An et al, 2017 ). The analysis was performed with the assay kit protocol.…”

Section: Methodsmentioning

confidence: 99%

Tortoise Plastron and Deer Antler Gelatin Prevents Against Neuronal Mitochondrial Dysfunction In Vitro: Implication for a Potential Therapy of Alzheimer’s Disease

et al. 2021

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Mitochondrial dysfunction with oxidative damage plays the fundamental roles in the pathogenesis of Alzheimer’s disease. In traditional Chinese medicine (TCM) practice, animal tissue-derived gelatins are often used as nootropic agents to treat cognitive deterioration and senile dementia. Tortoise plastron gelatin (TPG) and deer antler gelatin (DAG) are the two most commonly used gelatins for this purpose. This study sought to examine the effects of the two gelatins in preventing neuronal mitochondria from oxidative damage. PC12 cells, a cell line derived from rat pheochromocytoma, exposed to the neurotoxin Aβ25–35 served as an in vitro model of Alzheimer’s disease. The cells were separately pre-treated with TPG and DAG at various concentrations ranging from 6.26 µg/ml–200 µg/ml, followed by co-incubation with 20 μM Aβ25–35 for different duration. Cell viability, mitochondrial membrane potential (MMP) and ultrastructure, intracellular ATP, reactive oxygen species (ROS) and calcium (Ca2+) level, the expression of mitochondrial dynamic proteins and biomarkers of apoptosis were measured. Pretreatment with TPG and DAG reversed the Aβ-induced reduction of cell viability in a dose-dependent manner. Both TPG and DAG significantly increased MMP and ATP, alleviated the accumulation of damaged mitochondrial fragments, and normalized the aberrant expression of multiple mitochondrial dynamic proteins of the Aβ-exposed cells. Both gelatins also suppressed intracellular ROS overproduction and Ca2+ overload, overexpression of cytochrome c and pro-apoptosis biomarkers induced by the Aβ exposure. These results suggest that TPG and DAG may have the anti-dementia potential by preventing neuronal mitochondria from oxidative damage.

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Celastrol suppresses expression of adhesion molecules and chemokines by inhibiting JNK-STAT1/NF-κB activation in poly(I:C)-stimulated astrocytes

Cited by 23 publications

References 26 publications

Antitumor activity of celastrol by inhibition of proliferation, invasion, and migration in cholangiocarcinoma via PTEN/PI3K/Akt pathway

Antitumor activity of celastrol by inhibition of proliferation, invasion, and migration in cholangiocarcinoma via PTEN/PI3K/Akt pathway

Cadmium induces CCL2 production in glioblastoma cells via activation of MAPK, PI3K, and PKC pathways

Tortoise Plastron and Deer Antler Gelatin Prevents Against Neuronal Mitochondrial Dysfunction In Vitro: Implication for a Potential Therapy of Alzheimer’s Disease

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