Celastrol inhibits growth and metastasis of human gastric cancer cell MKN45 by down‐regulating microRNA‐21

Yao, Shanshan; Han, Lei; Tian, Zibin; Yu, Yang; Zhang, Qi; Li, Xiaoyü; Mao, Tao; Yang, Lin

doi:10.1002/ptr.6359

Cited by 34 publications

(17 citation statements)

References 39 publications

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“…Previous studies confer that Cel inhibits cancer growth, inflammation and cardiac fibrosis. 9,40,41 In the present study, we found that a new target (i.e. miR-345-5p) of Cel was activated in HG-stimulated cardiomyocyte, whereas Cel administration could neutralize HG-induced up-regulation of miR-345-5p expression.…”

Section: Discussionsupporting

confidence: 51%

Celastrol mitigates high glucose‐induced inflammation and apoptosis in rat H9c2 cardiomyocytes via miR‐345‐5p/growth arrest‐specific 6

Cao

Zhang

et al. 2020

The Journal of Gene Medicine

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Background Celastrol (Cel) has been corroborated as an anti‐inflammatory and anti‐apoptotic agent in multiple cell damage models. However, the protective effect of Cel in high glucose (HG)‐induced cardiomyocyte injury is still unclear. The present study aimed to determine whether Cel can mitigate HG‐stimulated cardiomyocyte injury via regulating the miR‐345‐5p/growth arrest‐specific 6 (Gas6) signaling pathway. Methods Cardiomyocytes were exposed to normal glucose (NG; 5 mmol/l) or HG (30 mmol/l) and then administered with Cel. Cell counting kit‐8 and flow cytometry assays were used to detect cell proliferative activity and apoptosis. mRNA and protein expression were analyzed using a quantitative reverse transcriptase‐polymerase chain reaction and western blotting, respectively. A bioinformatics algorithm and a luciferase reporter gene assay were used to determine whether Gas6 is a direct target of miR‐345‐5p. Results The present study confirmed the inhibitory effects of Cel in HG‐induced inflammation in cardiomyocytes. Moreover, Cel exhibited the ability to antagonize HG‐induced cardiomyocyte apoptosis and suppress the elevated Bax/Bcl‐2 ratio elicited by HG stimulation. Intriguingly, Cel treatment revoked the HG‐triggered repression of Gas6 protein expression, and Gas6 loss‐of‐function accelerated HG‐induced cardiomyocyte apoptosis. HG‐triggered up‐regulation of miR‐345‐5p expression was depressed following Cel treatment. Importantly, we validated that Gas6 is a direct target of miR‐345‐5p. Transfection with miR‐345‐5p inhibitors restrained HG‐induced release of pro‐inflammatory cytokines and cell apoptosis. Conclusions The findings of the present study demonstrate that Cel administration antagonized HG‐induced cardiomyocyte apoptosis and inflammation through up‐regulating Gas6 expression by restraining miR‐345‐5p.

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Section: Discussionsupporting

confidence: 51%

Celastrol mitigates high glucose‐induced inflammation and apoptosis in rat H9c2 cardiomyocytes via miR‐345‐5p/growth arrest‐specific 6

Cao

Zhang

et al. 2020

The Journal of Gene Medicine

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“…Celastrol possesses multiple pharmacological effects and showed potent anti-inflammatory effect against many disease models, [10][11][12][13] and however, few reports can be seen regarding the anti-inflammatory potential of celastrol in liver fibrosis. SIR2 is a family of histone deacetylases and is widely distributed in cells with multiple functions.…”

Section: The Active Ingredients Extracted From Traditional Chinesementioning

confidence: 99%

“…The active ingredients extracted from Traditional Chinese Medicine have become important choices for the treatment of several chronic diseases, including liver fibrosis . Celastrol is a pentacyclic triterpenoid compound (the chemical structure of celastrol is shown in Figure ), which is isolated from a common clinical used Traditional Chinese Medicine named Tripterygium wilfordii Hook F. Celastrol possesses multiple pharmacological effects and showed potent anti‐inflammatory effect against many disease models, and however, few reports can be seen regarding the anti‐inflammatory potential of celastrol in liver fibrosis. SIR2 is a family of histone deacetylases and is widely distributed in cells with multiple functions .…”

Section: Introductionmentioning

confidence: 99%

Celastrol exerts anti‐inflammatory effect in liver fibrosis via activation of AMPK‐SIRT3 signalling

Wang

et al. 2019

J Cellular Molecular Medi

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Celastrol, a pentacyclic tritepene extracted from Tripterygium Wilfordi plant, showing potent liver protection effects on several liver‐related diseases. However, the anti‐inflammatory potential of celastrol in liver fibrosis and the detailed mechanisms remain uncovered. This study was to investigate the anti‐inflammatory effect of celastrol in liver fibrosis and to further reveal mechanisms of celastrol‐induced anti‐inflammatory effects with a focus on AMPK‐SIRT3 signalling. Celastrol showed potent ameliorative effects on liver fibrosis both in activated hepatic stellate cells (HSCs) and in fibrotic liver. Celastrol remarkably suppressed inflammation in vivo and inhibited the secretion of inflammatory factors in vitro. Interestingly, celastrol increased SIRT3 promoter activity and SIRT3 expression both in fibrotic liver and in activated HSCs. Furthermore, SIRT3 silencing evidently ameliorated the anti‐inflammatory potential of celastrol. Besides, we found that celastrol could increase the AMPK phosphorylation. Further investigation showed that SIRT3 siRNA decreased SIRT3 expression but had no obvious effect on phosphorylation of AMPK. In addition, inhibition of AMPK by employing compound C (an AMPK inhibitor) or AMPK1α siRNA significantly suppressed SIRT3 expression, suggesting that AMPK was an up‐stream protein of SIRT3 in liver fibrosis. We further found that depletion of AMPK significantly attenuated the inhibitory effect of celastrol on inflammation. Collectively, celastrol attenuated liver fibrosis mainly through inhibition of inflammation by activating AMPK‐SIRT3 signalling, which makes celastrol be a potential candidate compound in treating or protecting against liver fibrosis.

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“…Some miRNAs, such as miR-4670-5p, miR-940, miR-493, miR-30e, and miR-7, have been shown to have antitumor effects both in vitro and in vivo, [99][100][101][102] and other miRNAs, such as miR-494, miR-124, miR-34a, miR-21, and miR-9, have been investigated in more than one study. [97][98][99][100][101][102][103][104][105][106][107][108][109][110][111][112][113][114]…”

Section: Microrna-based Other Therapiesmentioning

confidence: 99%

<p>Research Progress in microRNA-Based Therapy for Gastric Cancer</p>

Zhao

Shi

et al. 2019

OTT

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Gastric cancer (GC) is one of the leading causes of tumor-related mortality. In addition to surgery and endoscopic resection, systemic therapy remains the main treatment option for GC, especially for advanced-stage disease and for cases not suitable for surgical therapy. Hence, improving the efficacy of systemic therapy is still an urgent problem to overcome. In the past decade, the essential roles of microRNAs (miRNAs) in tumor treatment have been increasingly recognized. In particular, miRNAs were recently shown to reverse the resistance to chemotherapy drugs such as 5-fluorouracil, cisplatin, and doxorubicin. Synthesized nanoparticles loaded with mimics or inhibitors of miRNAs can directly target tumor cells to suppress their growth. Moreover, exosomes may serve as promising safe carriers for mimics or inhibitors of miRNAs to treat GC. Some miRNAs have also been shown to play roles in the mechanism of action of other anti-tumor drugs. Therefore, in this review, we highlight the research progress on microRNA-based therapy in GC and discuss the challenges and prospects associated with this strategy. We believe that microRNA-based therapy has the potential to offer a clinical benefit to GC patients, and this review would contribute to and motivate further research to promote this field toward this ultimate goal.

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Celastrol inhibits growth and metastasis of human gastric cancer cell MKN45 by down‐regulating microRNA‐21

Cited by 34 publications

References 39 publications

Celastrol mitigates high glucose‐induced inflammation and apoptosis in rat H9c2 cardiomyocytes via miR‐345‐5p/growth arrest‐specific 6

Celastrol mitigates high glucose‐induced inflammation and apoptosis in rat H9c2 cardiomyocytes via miR‐345‐5p/growth arrest‐specific 6

Celastrol exerts anti‐inflammatory effect in liver fibrosis via activation of AMPK‐SIRT3 signalling

<p>Research Progress in microRNA-Based Therapy for Gastric Cancer</p>

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