EGCG reverses human neutrophil elastase-induced migration in A549 cells by directly binding to HNE and by regulating α1-AT
Yilixiati Xiaokaiti, Haoming Wu, Ya Chen, Haopeng Yang, Jianhui Duan, Xin Li, Yan Pan, Lu Tie, Liangren Zhang, Xuejun Li
TL;DR
EGCG helps stop cancer cell movement by binding to an enzyme and boosting a natural inhibitor, offering a new way to fight lung cancer.
Contribution
EGCG reverses neutrophil elastase-induced migration by directly binding to HNE and upregulating α1-antitrypsin via the PI3K/Akt pathway.
Findings
EGCG directly binds to and inhibits neutrophil elastase enzymatic activity.
EGCG increases α1-antitrypsin expression in A549 cells.
The PI3K/Akt pathway may mediate α1-antitrypsin upregulation by EGCG.
Abstract
Lung carcinogenesis is a complex process that occurs in unregulated inflammatory environment. EGCG has been extensively investigated as a multi-targeting anti-tumor and anti-inflammatory compound. In this study, we demonstrated a novel mechanism by which EGCG reverses the neutrophil elastase-induced migration of A549 cells. We found that neutrophil elastase directly triggered human adenocarcinoma A549 cell migration and that EGCG suppressed the elevation of tumor cell migration induced by neutrophil elastase. We observed that EGCG directly binds to neutrophil elastase and inhibits its enzymatic activity based on the CDOCKER algorithm, MD stimulation by GROMACS, SPR assay and elastase enzymatic activity assay. As the natural inhibitor of neutrophil elastase, α1-antitrypsin is synthesized in tumor cells. We further demonstrated that the expression of α1-antitrypsin was up-regulated after…
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Taxonomy
TopicsMerger and Competition Analysis · Economic Theory and Institutions