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 (−)-ep...
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doaj-804bf9cc0a734ec6bd040410b368d4f92020-11-24T23:33:40ZengMDPI AGMolecules1420-30492018-08-01238207110.3390/molecules23082071molecules23082071Green Tea Catechin Is an Alternative Immune Checkpoint Inhibitor that Inhibits PD-L1 Expression and Lung Tumor GrowthAnchalee Rawangkan0Pattama Wongsirisin1Kozue Namiki2Keisuke Iida3Yasuhito Kobayashi4Yoshihiko Shimizu5Hirota Fujiki6Masami Suganuma7Graduate School of Science and Engineering, Saitama University, Saitama 338-8570, JapanGraduate School of Science and Engineering, Saitama University, Saitama 338-8570, JapanGraduate School of Science and Engineering, Saitama University, Saitama 338-8570, JapanMolecular Chirality Research Center and Department of Chemistry, Graduate School of Science, Chiba University, Chiba 263-8522, JapanSaitama Cardiovascular and Respiratory Center, Kumagaya, Saitama 360-0197, JapanSaitama Cardiovascular and Respiratory Center, Kumagaya, Saitama 360-0197, JapanFaculty of Medicine, Saga University, Saga 849-8501, JapanGraduate School of Science and Engineering, Saitama University, Saitama 338-8570, JapanThe 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.http://www.mdpi.com/1420-3049/23/8/2071(−)-epigallocatechin gallateimmune checkpointinterferon-γepidermal growth factorlung tumor |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anchalee Rawangkan Pattama Wongsirisin Kozue Namiki Keisuke Iida Yasuhito Kobayashi Yoshihiko Shimizu Hirota Fujiki Masami Suganuma |
spellingShingle |
Anchalee Rawangkan Pattama Wongsirisin Kozue Namiki Keisuke Iida Yasuhito Kobayashi Yoshihiko Shimizu Hirota Fujiki Masami Suganuma Green Tea Catechin Is an Alternative Immune Checkpoint Inhibitor that Inhibits PD-L1 Expression and Lung Tumor Growth Molecules (−)-epigallocatechin gallate immune checkpoint interferon-γ epidermal growth factor lung tumor |
author_facet |
Anchalee Rawangkan Pattama Wongsirisin Kozue Namiki Keisuke Iida Yasuhito Kobayashi Yoshihiko Shimizu Hirota Fujiki Masami Suganuma |
author_sort |
Anchalee Rawangkan |
title |
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_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_sort |
green tea catechin is an alternative immune checkpoint inhibitor that inhibits pd-l1 expression and lung tumor growth |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2018-08-01 |
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. |
topic |
(−)-epigallocatechin gallate immune checkpoint interferon-γ epidermal growth factor lung tumor |
url |
http://www.mdpi.com/1420-3049/23/8/2071 |
work_keys_str_mv |
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