Next Article in Journal
Antihyperalgesic Activity of Atomoxetine on Diabetes-Induced Neuropathic Pain: Contribution of Noradrenergic and Dopaminergic Systems
Next Article in Special Issue
Relationships between Structures of Condensed Tannins from Texas Legumes and Methane Production During In Vitro Rumen Digestion
Previous Article in Journal
Valorization of Olive Pomace-Based Nutraceuticals as Antioxidants in Chemical, Food, and Biological Models
Previous Article in Special Issue
Structural Revisions in Natural Ellagitannins
Article Menu
Issue 8 (August) cover image

Export Article

Open AccessArticle
Molecules 2018, 23(8), 2071;

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

Graduate School of Science and Engineering, Saitama University, Saitama 338-8570, Japan
Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama 362-0806, Japan
Molecular Chirality Research Center and Department of Chemistry, Graduate School of Science, Chiba University, Chiba 263-8522, Japan
Saitama Cardiovascular and Respiratory Center, Kumagaya, Saitama 360-0197, Japan
Faculty of Medicine, Saga University, Saga 849-8501, Japan
Author to whom correspondence should be addressed.
Academic Editor: Hideyuki Ito
Received: 20 July 2018 / Revised: 15 August 2018 / Accepted: 16 August 2018 / Published: 18 August 2018
Full-Text   |   PDF [2546 KB, uploaded 18 August 2018]   |  


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. View Full-Text
Keywords: (−)-epigallocatechin gallate; immune checkpoint; interferon-γ; epidermal growth factor; lung tumor (−)-epigallocatechin gallate; immune checkpoint; interferon-γ; epidermal growth factor; lung tumor

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material


Share & Cite This Article

MDPI and ACS Style

Rawangkan, A.; Wongsirisin, P.; Namiki, K.; Iida, K.; Kobayashi, Y.; Shimizu, Y.; Fujiki, H.; Suganuma, M. Green Tea Catechin Is an Alternative Immune Checkpoint Inhibitor that Inhibits PD-L1 Expression and Lung Tumor Growth. Molecules 2018, 23, 2071.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top