Salidroside Suppresses the Proliferation and Migration of Human Lung Cancer Cells through AMPK-Dependent NLRP3 Inflammasome Regulation.

Abstract

Inflammatory reactions mediated by the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome contributes to non-small-cell lung cancer (NSCLC) progression, particularly in patients with bacterial infections. Salidroside (SAL) has recently been shown to suppress lipopolysaccharide- (LPS-) induced NSCLC proliferation and migration, but its mechanism of action remains unclear. It has been shown that SAL improves metabolic inflammation in diabetic rodents through AMP-activated protein kinase- (AMPK-) dependent inhibition of the NLRP3 inflammasome. However, whether the NLRP3 inflammasome is regulated by SAL in NSCLC cells and how its underlying mechanism(s) can be determined require clarification. In this study, human lung alveolar basal carcinoma epithelial (A549) cells were treated with LPS, and the effects of SAL on cell proliferation, migration, AMPK activity, reactive oxygen species (ROS) production, and NLRP3 inflammasome activation were investigated. We found that LPS induction increases the proliferation and migration of A549 cells which was suppressed by SAL. Moreover, SAL protected A549 cells against LPS-induced AMPK inhibition, ROS production, and NLRP3 inflammasome activation. Blocking AMPK using Compound C almost completely suppressed the beneficial effects of SAL. In summary, these results indicate that SAL suppresses the proliferation and migration of human lung cancer cells through AMPK-dependent NLRP3 inflammasome regulation.

• Authors: Weidong Ma, Ziyuan Wang, Yan Zhao, Qibin Wang, Yonghong Zhang, Pan Lei, Wei Lu, Shan Yan, Jun Zhou, Xiaojiao Li, Wenjun Yu, Yaoxin Zhong, Li Chen, Tao Zheng
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2021 Pg. 6614574 ( 2021) ISSN: 1942-0994 [Electronic] United States
• PMID: 34457117 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Weidong Ma et al.

Chemical References

• Glucosides
• Inflammasomes
• Lipopolysaccharides
• NLR Family, Pyrin Domain-Containing 3 Protein
• NLRP3 protein, human
• Phenols
• Reactive Oxygen Species
• AMP-Activated Protein Kinases
• rhodioloside

Topics

• AMP-Activated Protein Kinases (metabolism)
• Apoptosis
• Carcinoma, Non-Small-Cell Lung (drug therapy, immunology, metabolism, pathology)
• Cell Movement
• Cell Proliferation
• Glucosides (pharmacology)
• Humans
• Inflammasomes (drug effects, metabolism)
• Lipopolysaccharides (pharmacology)
• Lung Neoplasms (drug therapy, immunology, metabolism, pathology)
• NLR Family, Pyrin Domain-Containing 3 Protein (genetics, metabolism)
• Phenols (pharmacology)
• Reactive Oxygen Species (metabolism)
• Signal Transduction
• Tumor Cells, Cultured