Biological Evaluation of Alkyl Triphenylphosphonium Ostruthin Derivatives as Potential Anti-Inflammatory Agents Targeting the Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells
| Autor: | Takao Kataoka, Nghia Trong Vo, Sayaka Haruyama, Chihiro Moriwaki, Nhan Trung Nguyen, Eiichi Kusagawa, Sayuri Fukuhara, Mai Thanh Thi Nguyen, Yasunobu Miyake, Kaori Nakano, Phu Hoang Dang |
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| Rok vydání: | 2021 |
| Předmět: |
A549 cell
Chemistry Kinase ostruthin General Medicine coumarin Molecular biology triphenylphosphonium (TPP) tumor necrosis factor-α (TNF-α) intercellular adhesion molecule-1 (ICAM-1) nuclear factor κB (NF-κB) Phosphorylation Tumor necrosis factor alpha Viability assay Signal transduction Cytotoxicity Chromatin immunoprecipitation |
| Zdroj: | BioChem Volume 1 Issue 2 Pages 10-121 |
| ISSN: | 2673-6411 |
| DOI: | 10.3390/biochem1020010 |
| Popis: | Ostruthin (6-geranyl-7-hydroxycoumarin) is one of the constituents isolated from Paramignya trimera and has been classified as a simple coumarin. We recently reported the synthesis of alkyl triphenylphosphonium (TPP) derivatives from ostruthin and evaluated their anticancer activities. In the present study, we demonstrated that alkyl TPP ostruthin derivatives inhibited the up-regulation of cell-surface intercellular adhesion molecule-1 (ICAM-1) in human lung adenocarcinoma A549 cells stimulated with tumor necrosis factor-α (TNF-α) without affecting cell viability, while ostruthin itself exerted cytotoxicity against A549 cells. The heptyl TPP ostruthin derivative (termed OS8) attenuated the up-regulation of ICAM-1 mRNA expression at concentrations higher than 40 µM in TNF-α-stimulated A549 cells. OS8 inhibited TNF-α-induced nuclear factor κB (NF-κB)-responsive luciferase reporter activity at concentrations higher than 40 µM, but did not affect the translocation of the NF-κB subunit RelA in response to the TNF-α stimulation at concentrations up to 100 µM. A chromatin immunoprecipitation assay showed that OS8 at 100 µM prevented the binding of RelA to the ICAM-1 promoter. We also showed that OS8 at 100 µM inhibited the TNF-α-induced phosphorylation of RelA at Ser 536. Moreover, the TNF-α-induced phosphorylation of an inhibitor of NF-κB α and extracellular signal-regulated kinase was reduced by OS8. These results indicate that OS8 has potential as an anti-inflammatory agent that targets the NF-κB signaling pathway. |
| Databáze: | OpenAIRE |
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