Microsomal prostaglandin E2 synthase-1 and its inhibitors: Molecular mechanisms and therapeutic significance

Zhang, Yanyu; Yao, Yun-Da; Luo, Jin-Fang; Liu, Zhongqiu; Huang, Yuming; Wu, Feichi; Sun, Qin-Hua; Liu, Jianxin; Zhou, Hua

doi:10.1016/j.phrs.2021.105977

Cited by 19 publications

(12 citation statements)

References 166 publications

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“…Other key molecules included Y-box binding protein 1 (YB-1) (22), NF-κB, etc. (39). In our group, we reported that c-Jun N-terminal kinase served a role in the mPGES-1/PGE2/EP4/MAPK positive feedback loops in T-ALL cells.…”

Section: Abnormal Activation Of Specific Jak/stat Signal Results Inmentioning

confidence: 91%

Growth of T-cell lymphoma cells is inhibited by mPGES-1/PGE2 suppression via JAK/STAT, TGF-β/Smad3 and PI3K/AKT signal pathways

Li¹,

Meng²,

Li³

et al. 2022

Transl Cancer Res TCR

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Background: T-cell lymphoma (TCL) has a very poor prognosis with limited treatment options and novel therapeutic target is urgently needed. Our previous studies have found that suppression of membrane-bound prostaglandin E2 synthase l/prostaglandin E2 (mPGES-1/PGE2) exerted anti-neoplastic effects in leukemia cells by suppressing AKT signal pathway. Here, we aim at evaluating the role and mechanism of mPGES-1/ PGE2 signaling in TCL.Methods: Expression of mPGES-1 in TCL cell line Hut78 was analyzed by Western blot and immunofluorescence. CAY10526, a selective mPGES-1 inhibitor, was used to treat Hut 78 cells. Cell viability assays was performed by using cell counting kit-8 (CCK-8). Cell apoptosis rate was examined by flow cytometer. PGE2 synthesis was detected by enzyme immunoassay (EIA). The expression of mPGES-1, cleaved caspase-3, Janus kinase/signal transduction and transcription (JAK/STAT), transforming growth factor-β (TGF-β)/Smad3 and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway of Hut 78 cells after exposed to CAY10526 was analyzed by Western blot.Results: mPGES-1 was highly expressed in Hut78 cell compared to normal peripheral blood mononuclear cells. CAY10526 inhibited cell proliferation and induced apoptosis in Hut78 cells. These effects may be partially attributed to the activation of the Caspase family and the inhibition of JAK/STAT, TGF-β/ Smad3 and PI3K/AKT signal pathways.Conclusions: Our results suggested that mPGES-1/PGE2 could be a potential therapeutic target for TCL.

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Section: Abnormal Activation Of Specific Jak/stat Signal Results Inmentioning

confidence: 91%

Growth of T-cell lymphoma cells is inhibited by mPGES-1/PGE2 suppression via JAK/STAT, TGF-β/Smad3 and PI3K/AKT signal pathways

Li¹,

Meng²,

Li³

et al. 2022

Transl Cancer Res TCR

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“…It plays a critical role in prostaglandin synthesis and inflammation. As COX‐2 enzyme inhibitors, non‐steroidal anti‐inflammatory drugs are widely used to reduce the production of prostaglandin E2 to alleviate inflammatory reactions [20]. MMPs are widely involved in cellular differentiation, inflammation, and angiogenesis [21].…”

Section: Resultsmentioning

confidence: 99%

Uncovering the effective substances and mechanism of Ipomoea pes‐caprae against rheumatoid arthritis using liquid chromatography‐mass spectrometry and targeted network pharmacology

Cheng

Cui

Hou

et al. 2023

J of Separation Science

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Ipomoea pes-caprae (L.) R. Br (Convolvulaceae) is a commonly used marine traditional Chinese medicine in the southern coastal areas of China. It has been widely used to treat rheumatoid arthritis, but its effective substances and antirheumatoid arthritis mechanism remain ambiguous. Hence, in this study, the chemical profile and absorbed ingredients of Ipomoea pes-caprae were elucidated by ultra-performance liquid chromatography-mass spectrometry. Moreover, targeted network pharmacology was used to clarify the mechanism of action of Ipomoea pes-caprae in treating rheumatoid arthritis. Finally, 23 compounds were identified in the aqueous extracts of Ipomoea pes-caprae and 12 absorbed ingredients were detected in rats' plasma. These 12 absorbed ingredients might be the essential effective substances of Ipomoea pes-caprae. The tissue distributions of 3 absorbed ingredients in rats were successfully analyzed. The targeted network pharmacological analysis results indicated that the regulation of inflammatory reaction, immune response, cell proliferation, and apoptosis were the critical mechanism of Ipomoea pes-caprae against rheumatoid arthritis. This study successfully clarified the effective substances and potential mechanisms of Ipomoea pes-caprae in treating rheumatoid arthritis. The results of this research could provide a valuable reference for further scientific research and clinical application.Article Related Abbreviations: AIA, adjuvant-induced arthritis; CFA, complete Freund's adjuvant; CYP450, cytochrome P450; FLSs, fibroblast-like synoviocytes; KEGG, Kyoto Encyclopedia of Genes and Genomes; RA, rheumatoid arthritis; TNF, tumor necrosis factor; UPLC Q-TOF-MS, ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry; UPLC-TQ-MS, ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry.

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“…Furthermore, the production of all PGs, such as prostaglandin D2 (PGD2), PGE2, prostaglandin F2α (PGF2α), prostacyclin (PGI2), and thromboxane A2 (TXA2), occurs by the action of different specific terminal synthases [ 42 ]. PGE2 is synthesized through the action of three different prostaglandin E2 synthases (PGESs).…”

Section: Prostaglandin E2mentioning

confidence: 99%

Cooperation between Prostaglandin E2 and Epidermal Growth Factor Receptor in Cancer Progression: A Dual Target for Cancer Therapy

Finetti

Paradisi

Bernardi

et al. 2023

Cancers

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It is recognized that prostaglandin E2 (PGE2) is one key lipid mediator involved in chronic inflammation, and it is directly implicated in tumor development by regulating cancer cell growth and migration, apoptosis, epithelial–mesenchymal transition, angiogenesis, and immune escape. In addition, the expression of the enzymes involved in PGE2 synthesis, cyclooxygenase 2 (COX-2) and microsomal prostaglandin E synthase 1 (mPGES1), positively correlates with tumor progression and aggressiveness, clearly indicating the crucial role of the entire pathway in cancer. Moreover, several lines of evidence suggest that the COX2/mPGES1/PGE2 inflammatory axis is involved in the modulation of epidermal growth factor receptor (EGFR) signaling to reinforce the oncogenic drive of EGFR activation. Similarly, EGFR activation promotes the induction of COX2/mPGES1 expression and PGE2 production. In this review, we describe the interplay between COX2/mPGES1/PGE2 and EGFR in cancer, and new therapeutic strategies that target this signaling pathway, to outline the importance of the modulation of the inflammatory process in cancer fighting.

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Microsomal prostaglandin E2 synthase-1 and its inhibitors: Molecular mechanisms and therapeutic significance

Cited by 19 publications

References 166 publications

Growth of T-cell lymphoma cells is inhibited by mPGES-1/PGE2 suppression via JAK/STAT, TGF-β/Smad3 and PI3K/AKT signal pathways

Growth of T-cell lymphoma cells is inhibited by mPGES-1/PGE2 suppression via JAK/STAT, TGF-β/Smad3 and PI3K/AKT signal pathways

Uncovering the effective substances and mechanism of Ipomoea pes‐caprae against rheumatoid arthritis using liquid chromatography‐mass spectrometry and targeted network pharmacology

Cooperation between Prostaglandin E2 and Epidermal Growth Factor Receptor in Cancer Progression: A Dual Target for Cancer Therapy

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