UM  > Institute of Chinese Medical Sciences
Licochalcone A inhibits interferon-gamma-induced programmed death-ligand 1 in lung cancer cells
Yuan,Luo Wei1; Jiang,Xiao Ming1; Xu,Yu Lian1; Huang,Mu Yang1; Chen,Yu Chi1; Yu,Wei Bang1; Su,Min Xia1; Ye,Zi Han1; Chen,Xiuping1; Wang,Yitao1; Lu,Jin Jian1,2
2021
Source PublicationPhytomedicine
ISSN0944-7113
Volume80
AbstractBackground: Programmed death-ligand 1 (PD-L1), which can be induced by interferon-gamma (IFN-γ) in the tumor microenvironment, is a critical immune checkpoint in cancer immunotherapy. Natural products which reduce IFN-γ-induced PD-L1 might be exert immunotherapy effect. Licochalcone A (LCA), a natural compound derived from the root of Glycyrrhiza inflata Batalin. (Fabaceae), was found to interfere IFN-γ-induced PD-L1. Purpose: The aim of this study is to further clarify the effect and the mechanism of LCA on inhibiting IFN-γ-induced PD-L1 in lung cancer cells. Methods: The expression levels of PD-L1 were evaluated by flow cytometry, western blot and qRT-PCR. Click-iT protein synthesis assay and luciferase assay were used to identify the effect of LCA on protein synthesis. Jurkat T cell proliferation and apoptosis in the co-culture system were detected by flow cytometry. Flow cytometry was also applied to evaluate reactive oxygen species (ROS) generation. Results: LCA downregulated IFN-γ-induced PD-L1 protein expression and membrane localization in human lung cancer cells, regardless of inhibiting PD-L1 mRNA level or promoting its protein degradation. LCA decreased apoptosis and proliferative inhibition of Jurkat T cells caused by IFN-γ-induced PD-L1-expressing in A549 cells in the co-culture system. Strikingly, LCA was verified as a protein synthesis inhibitor, which reduced both cap-dependent and -independent translation. LCA inhibited PD-L1 translation, likely due to inhibition of 4EBP1 phosphorylation (Ser 65) and activation of PERK-eIF2α pathway. Furthermore, LCA induced ROS generation in a time-dependent manner in lung cancer cells. N-acetyl-L-cysteine (NAC) not only revered ROS generation triggered by LCA but also restored IFN-γ-induced expression of PD-L1. Both the inhibition of 4EBP1 phosphorylation (Ser 65) and activation of PERK-eIF2α axis triggered by LCA was restored by co-treatment with NAC. Conclusion: LCA abrogated IFN-γ-induced PD-L1 expression via ROS generation to abolish the protein translation, indicating that LCA has the potential to be applied in cancer immunotherapy.
KeywordIFN-γ Licochalcone A Natural products PD-L1 Protein synthesis inhibitor ROS
DOI10.1016/j.phymed.2020.153394
URLView the original
Language英语
Fulltext Access
Citation statistics
Cited Times [WOS]:0   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences,University of Macau,Macao,China
2.State Key Laboratory of Natural Medicines,China Pharmaceutical University,Nanjing,210009,China
First Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Yuan,Luo Wei,Jiang,Xiao Ming,Xu,Yu Lian,et al. Licochalcone A inhibits interferon-gamma-induced programmed death-ligand 1 in lung cancer cells[J]. Phytomedicine,2021,80.
APA Yuan,Luo Wei.,Jiang,Xiao Ming.,Xu,Yu Lian.,Huang,Mu Yang.,Chen,Yu Chi.,...&Lu,Jin Jian.(2021).Licochalcone A inhibits interferon-gamma-induced programmed death-ligand 1 in lung cancer cells.Phytomedicine,80.
MLA Yuan,Luo Wei,et al."Licochalcone A inhibits interferon-gamma-induced programmed death-ligand 1 in lung cancer cells".Phytomedicine 80(2021).
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Yuan,Luo Wei]'s Articles
[Jiang,Xiao Ming]'s Articles
[Xu,Yu Lian]'s Articles
Baidu academic
Similar articles in Baidu academic
[Yuan,Luo Wei]'s Articles
[Jiang,Xiao Ming]'s Articles
[Xu,Yu Lian]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Yuan,Luo Wei]'s Articles
[Jiang,Xiao Ming]'s Articles
[Xu,Yu Lian]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.