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Isosinensetin alleviates the injury of human bronchial epithelial cells induced by PM_2.5.

ABSTRACT: Flavonoids which are extracted from citrus peel and pulp have been reported to have multiple beneficial effects on human health. Isosinensetin (ISO) is a type of flavonoid compound, which has several protective effects including anticancer, antioxidant, antiviral, anti-inflammatory and bacteriostatic. However, the molecular mechanism of its antioxidant and anti-inflammatory effects remain unclear. The present study aimed to investigate the intervention effect and possible mechanism of ISO on human bronchial epithelial cells injured by fine particular matter ≤2.5 µm in diameter (PM_2.5). In the present study, the cell viability was detected by Cell Counting Kit-8 method. The levels of pro-inflammatory cytokines were analyzed by ELISA. The level of reactive oxygen species (ROS) was detected by fluorescence probe. The expression levels of proliferating cell nuclear antigen (PCNA), nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor кΒ (NF-кB) proteins were detected by western blotting. The results revealed that ISO evidently increased the viability of 16-HBE cells and sharply decreased the levels of pro-inflammatory factors in cell culture supernatant. ISO significantly inhibited ROS release caused by PM_2.5. Moreover, the expression levels of PCNA, Nrf2 and NF-кB proteins were downregulated after ISO incubation. These results indicated that ISO alleviated 16-HBE-cell injury by PM_2.5 through the ROS-Nrf2/NF-кB signaling pathway.

SUBMITTER: Zou Y

PROVIDER: S-EPMC8543438 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Isosinensetin alleviates the injury of human bronchial epithelial cells induced by PM<sub>2.5</sub>.

Zou Yang Y Li Shuzhen S Li Xinming X Sun Ye Y Ma Mingyue M Tian Han H Wang Nan N Yuan Jianhui J Xiao Chunling C

Experimental and therapeutic medicine 20211011 6

Flavonoids which are extracted from citrus peel and pulp have been reported to have multiple beneficial effects on human health. Isosinensetin (ISO) is a type of flavonoid compound, which has several protective effects including anticancer, antioxidant, antiviral, anti-inflammatory and bacteriostatic. However, the molecular mechanism of its antioxidant and anti-inflammatory effects remain unclear. The present study aimed to investigate the intervention effect and possible mechanism of ISO on hum ...[more]

PMID: 34707716

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Project description:BackgroundTranslationally controlled tumor protein (TCTP) is linked to lung cancer. However, upon lung cancer carcinogens stimulation, there were no reports on the relationship between TCTP and lung cell carcinogenic epithelial-mesenchymal transition (EMT). This study was designed to investigate the molecular mechanism of regulation of TCTP expression and its role in lung carcinogens-induced EMT.MethodsTo study the role of TCTP in lung carcinogens [particulate matter 2.5 (PM2.5) or 4-methylnitrosamino-l-3-pyridyl-butanone (NNK)]-induced EMT, PM2.5/NNK-treated lung epithelial and non-small cell lung cancer (NSCLC) cells were tested. Cell derived xenografts, human lung cancer samples and online survival analysis were used to confirm the results. MassArray assay, Real-time PCR and Reporter assays were performed to elucidate the mechanism of regulation of TCTP expression. All statistical analyses were performed using GraphPad Prism version 6.0 or SPSS version 20.0.ResultsTranslationally controlled tumor protein and vimentin expression were up-regulated in PM2.5/NNK-treated lung cells and orthotopic implantation tumors. TCTP expression was positively correlated with vimentin in human NSCLC samples. Patients with high expression of TCTP displayed reduced overall and disease-free survival. TCTP overexpression could increase vimentin expression and promote cell metastasis. Furthermore, PM2.5/NNK stimulation brought a synergistic effect on EMT in TCTP-transfected cells. TCTP knockdown blocked PM2.5/NNK carcinogenic effect. Mechanically, PM2.5/NNK-induced TCTP expression was regulated by one microRNA, namely miR-125a-3p, but not by methylation on TCTP gene promoter. The level of TCTP was regulated by its specific microRNA during the process of PM2.5/NNK stimulation, which in turn enhanced vimentin expression and played a permissive role in carcinogenic EMT.ConclusionsOur results provided new insights into the mechanisms of TCTP regulatory expression in lung carcinogens-induced EMT. TCTP and miR-125a-3p might act as potential prognostic biomarkers and therapeutic targets for NSCLC.

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Isosinensetin alleviates the injury of human bronchial epithelial cells induced by PM_2.5.

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Isosinensetin alleviates the injury of human bronchial epithelial cells induced by PM<sub>2.5</sub>.

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Isosinensetin alleviates the injury of human bronchial epithelial cells induced by PM2.5.

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Isosinensetin alleviates the injury of human bronchial epithelial cells induced by PM<sub>2.5</sub>.

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OmicsDI is part of the ELIXIR infrastructure

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Isosinensetin alleviates the injury of human bronchial epithelial cells induced by PM_2.5.