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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...

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Autores principales: Rawangkan, Anchalee, Wongsirisin, Pattama, Namiki, Kozue, Iida, Keisuke, Kobayashi, Yasuhito, Shimizu, Yoshihiko, Fujiki, Hirota, Suganuma, Masami
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
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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.
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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
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