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Celastrol elicits antitumor effects by inhibiting the STAT3 pathway through ROS accumulation in non-small cell lung cancer.

Authors :
Zhao Z
Wang Y
Gong Y
Wang X
Zhang L
Zhao H
Li J
Zhu J
Huang X
Zhao C
Yang L
Wang L
Source :
Journal of translational medicine [J Transl Med] 2022 Nov 12; Vol. 20 (1), pp. 525. Date of Electronic Publication: 2022 Nov 12.
Publication Year :
2022

Abstract

Background: Non-small cell lung cancer (NSCLC) is the most common lung cancer with high mortality across the world, but it is challenging to develop an effective therapy for NSCLC. Celastrol is a natural bioactive compound, which has been found to possess potential antitumor activity. However, the underlying molecular mechanisms of celastrol activity in NSCLC remain elusive.<br />Methods: Cellular function assays were performed to study the suppressive role of celastrol in human NSCLC cells (H460, PC-9, and H520) and human bronchial epithelial cells BEAS-2B. Cell apoptosis levels were analyzed by flow cytometry, Hoechst 33342, caspase-3 activity analysis, and western blot analysis. Intracellular reactive oxygen species (ROS) were analyzed by flow cytometry and fluorescence microscope. Expression levels of endoplasmic reticulum (ER) stress-related proteins and phosphorylated signal transducer and activator of transcription 3 (P-STAT3) were identified via western blot analysis. A heterograft model in nude mice was employed to evaluate the effect of celastrol in vivo.<br />Results: Celastrol suppressed the growth, proliferation, and metastasis of NSCLC cells. Celastrol significantly increased the level of intracellular ROS; thus, triggering the activation of the ER stress pathway and inhibition of the P-STAT3 pathway, and eventually leading to cell apoptosis, and the effects were reversed by the pre-treatment with N-Acetyl-L-cysteine (NAC). Celastrol also suppressed tumor growth in vivo.<br />Conclusion: The outcomes revealed that celastrol plays a potent suppressive role in NSCLC in vitro and in vivo. Celastrol induces apoptosis via causing mitochondrial ROS accumulation to suppress the STAT3 pathway. Celastrol may have potential application prospects in the therapy of NSCLC.<br /> (© 2022. The Author(s).)

Details

Language :
English
ISSN :
1479-5876
Volume :
20
Issue :
1
Database :
MEDLINE
Journal :
Journal of translational medicine
Publication Type :
Academic Journal
Accession number :
36371217
Full Text :
https://doi.org/10.1186/s12967-022-03741-9