Cargando…
Green Tea Catechin Is an Alternative Immune Checkpoint Inhibitor that Inhibits PD-L1 Expression and Lung Tumor Growth
The anticancer activity of immune checkpoint inhibitors is attracting attention in various clinical sites. Since green tea catechin has cancer-preventive activity in humans, whether green tea catechin supports the role of immune checkpoint inhibitors was studied. We here report that (−)-epigallocate...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222340/ https://www.ncbi.nlm.nih.gov/pubmed/30126206 http://dx.doi.org/10.3390/molecules23082071 |
_version_ | 1783369183932710912 |
---|---|
author | Rawangkan, Anchalee Wongsirisin, Pattama Namiki, Kozue Iida, Keisuke Kobayashi, Yasuhito Shimizu, Yoshihiko Fujiki, Hirota Suganuma, Masami |
author_facet | Rawangkan, Anchalee Wongsirisin, Pattama Namiki, Kozue Iida, Keisuke Kobayashi, Yasuhito Shimizu, Yoshihiko Fujiki, Hirota Suganuma, Masami |
author_sort | Rawangkan, Anchalee |
collection | PubMed |
description | The anticancer activity of immune checkpoint inhibitors is attracting attention in various clinical sites. Since green tea catechin has cancer-preventive activity in humans, whether green tea catechin supports the role of immune checkpoint inhibitors was studied. We here report that (−)-epigallocatechin gallate (EGCG) inhibited programmed cell death ligand 1 (PD-L1) expression in non–small-cell lung cancer cells, induced by both interferon (IFN)-γ and epidermal growth factor (EGF). The mRNA and protein levels of IFN-γ–induced PD-L1 were reduced 40–80% after pretreatment with EGCG and green tea extract (GTE) in A549 cells, via inhibition of JAK2/STAT1 signaling. Similarly, EGF-induced PD-L1 expression was reduced about 37–50% in EGCG-pretreated Lu99 cells through inhibition of EGF receptor/Akt signaling. Furthermore, 0.3% GTE in drinking water reduced the average number of tumors per mouse from 4.1 ± 0.5 to 2.6 ± 0.4 and the percentage of PD-L1 positive cells from 9.6% to 2.9%, a decrease of 70%, in lung tumors of A/J mice given a single intraperitoneal injection of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In co-culture experiments using F10-OVA melanoma cells and tumor-specific CD3+ T cells, EGCG reduced PD-L1 mRNA expression about 30% in F10-OVA cells and restored interleukin-2 mRNA expression in tumor-specific CD3+ T cells. The results show that green tea catechin is an immune checkpoint inhibitor. |
format | Online Article Text |
id | pubmed-6222340 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62223402018-11-13 Green Tea Catechin Is an Alternative Immune Checkpoint Inhibitor that Inhibits PD-L1 Expression and Lung Tumor Growth Rawangkan, Anchalee Wongsirisin, Pattama Namiki, Kozue Iida, Keisuke Kobayashi, Yasuhito Shimizu, Yoshihiko Fujiki, Hirota Suganuma, Masami Molecules Article The anticancer activity of immune checkpoint inhibitors is attracting attention in various clinical sites. Since green tea catechin has cancer-preventive activity in humans, whether green tea catechin supports the role of immune checkpoint inhibitors was studied. We here report that (−)-epigallocatechin gallate (EGCG) inhibited programmed cell death ligand 1 (PD-L1) expression in non–small-cell lung cancer cells, induced by both interferon (IFN)-γ and epidermal growth factor (EGF). The mRNA and protein levels of IFN-γ–induced PD-L1 were reduced 40–80% after pretreatment with EGCG and green tea extract (GTE) in A549 cells, via inhibition of JAK2/STAT1 signaling. Similarly, EGF-induced PD-L1 expression was reduced about 37–50% in EGCG-pretreated Lu99 cells through inhibition of EGF receptor/Akt signaling. Furthermore, 0.3% GTE in drinking water reduced the average number of tumors per mouse from 4.1 ± 0.5 to 2.6 ± 0.4 and the percentage of PD-L1 positive cells from 9.6% to 2.9%, a decrease of 70%, in lung tumors of A/J mice given a single intraperitoneal injection of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In co-culture experiments using F10-OVA melanoma cells and tumor-specific CD3+ T cells, EGCG reduced PD-L1 mRNA expression about 30% in F10-OVA cells and restored interleukin-2 mRNA expression in tumor-specific CD3+ T cells. The results show that green tea catechin is an immune checkpoint inhibitor. MDPI 2018-08-18 /pmc/articles/PMC6222340/ /pubmed/30126206 http://dx.doi.org/10.3390/molecules23082071 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Rawangkan, Anchalee Wongsirisin, Pattama Namiki, Kozue Iida, Keisuke Kobayashi, Yasuhito Shimizu, Yoshihiko Fujiki, Hirota Suganuma, Masami Green Tea Catechin Is an Alternative Immune Checkpoint Inhibitor that Inhibits PD-L1 Expression and Lung Tumor Growth |
title | Green Tea Catechin Is an Alternative Immune Checkpoint Inhibitor that Inhibits PD-L1 Expression and Lung Tumor Growth |
title_full | Green Tea Catechin Is an Alternative Immune Checkpoint Inhibitor that Inhibits PD-L1 Expression and Lung Tumor Growth |
title_fullStr | Green Tea Catechin Is an Alternative Immune Checkpoint Inhibitor that Inhibits PD-L1 Expression and Lung Tumor Growth |
title_full_unstemmed | Green Tea Catechin Is an Alternative Immune Checkpoint Inhibitor that Inhibits PD-L1 Expression and Lung Tumor Growth |
title_short | Green Tea Catechin Is an Alternative Immune Checkpoint Inhibitor that Inhibits PD-L1 Expression and Lung Tumor Growth |
title_sort | green tea catechin is an alternative immune checkpoint inhibitor that inhibits pd-l1 expression and lung tumor growth |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222340/ https://www.ncbi.nlm.nih.gov/pubmed/30126206 http://dx.doi.org/10.3390/molecules23082071 |
work_keys_str_mv | AT rawangkananchalee greenteacatechinisanalternativeimmunecheckpointinhibitorthatinhibitspdl1expressionandlungtumorgrowth AT wongsirisinpattama greenteacatechinisanalternativeimmunecheckpointinhibitorthatinhibitspdl1expressionandlungtumorgrowth AT namikikozue greenteacatechinisanalternativeimmunecheckpointinhibitorthatinhibitspdl1expressionandlungtumorgrowth AT iidakeisuke greenteacatechinisanalternativeimmunecheckpointinhibitorthatinhibitspdl1expressionandlungtumorgrowth AT kobayashiyasuhito greenteacatechinisanalternativeimmunecheckpointinhibitorthatinhibitspdl1expressionandlungtumorgrowth AT shimizuyoshihiko greenteacatechinisanalternativeimmunecheckpointinhibitorthatinhibitspdl1expressionandlungtumorgrowth AT fujikihirota greenteacatechinisanalternativeimmunecheckpointinhibitorthatinhibitspdl1expressionandlungtumorgrowth AT suganumamasami greenteacatechinisanalternativeimmunecheckpointinhibitorthatinhibitspdl1expressionandlungtumorgrowth |