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Molecules. 2018 Aug 18;23(8). pii: E2071. doi: 10.3390/molecules23082071.

Green Tea Catechin Is an Alternative Immune Checkpoint Inhibitor that Inhibits PD-L1 Expression and Lung Tumor Growth.

Author information

1
Graduate School of Science and Engineering, Saitama University, Saitama 338-8570, Japan. ewmedsci@gmail.com.
2
Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama 362-0806, Japan. ewmedsci@gmail.com.
3
Graduate School of Science and Engineering, Saitama University, Saitama 338-8570, Japan. wongsiri.patt@gmail.com.
4
Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama 362-0806, Japan. wongsiri.patt@gmail.com.
5
Graduate School of Science and Engineering, Saitama University, Saitama 338-8570, Japan. k.namiki1080@gmail.com.
6
Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama 362-0806, Japan. k.namiki1080@gmail.com.
7
Molecular Chirality Research Center and Department of Chemistry, Graduate School of Science, Chiba University, Chiba 263-8522, Japan. kiida@chiba-u.jp.
8
Saitama Cardiovascular and Respiratory Center, Kumagaya, Saitama 360-0197, Japan. kobayashiyasuhito@yahoo.co.jp.
9
Saitama Cardiovascular and Respiratory Center, Kumagaya, Saitama 360-0197, Japan. shimizu.yoshihiko@pref.saitama.lg.jp.
10
Faculty of Medicine, Saga University, Saga 849-8501, Japan. uv4h-fjk@asahi-net.or.jp.
11
Graduate School of Science and Engineering, Saitama University, Saitama 338-8570, Japan. masami0306@mail.saitama-u.ac.jp.
12
Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama 362-0806, Japan. masami0306@mail.saitama-u.ac.jp.

Abstract

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.

KEYWORDS:

(−)-epigallocatechin gallate; epidermal growth factor; immune checkpoint; interferon-γ; lung tumor

PMID:
30126206
PMCID:
PMC6222340
DOI:
10.3390/molecules23082071
[Indexed for MEDLINE]
Free PMC Article

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