| RRC ID |
56061
|
| 著者 |
Rawangkan A, Wongsirisin P, Namiki K, Iida K, Kobayashi Y, Shimizu Y, Fujiki H, Suganuma M.
|
| タイトル |
Green Tea Catechin Is an Alternative Immune Checkpoint Inhibitor that Inhibits PD-L1 Expression and Lung Tumor Growth.
|
| ジャーナル |
Molecules
|
| 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.
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| 巻・号 |
23(8)
|
| 公開日 |
2018-8-18
|
| DOI |
10.3390/molecules23082071
|
| PII |
molecules23082071
|
| PMID |
30126206
|
| PMC |
PMC6222340
|
| MeSH |
Animals
Antineoplastic Agents, Phytogenic / chemistry
Antineoplastic Agents, Phytogenic / pharmacology*
B7-H1 Antigen / antagonists & inhibitors*
Catechin / chemistry
Catechin / pharmacology*
Cell Line, Tumor
Disease Models, Animal
Gene Expression
Humans
Immunomodulation / drug effects*
Lung Neoplasms / genetics
Lung Neoplasms / immunology
Lung Neoplasms / metabolism
Lung Neoplasms / pathology
Mice
Phosphorylation
Proto-Oncogene Proteins c-akt / metabolism
STAT1 Transcription Factor / metabolism
Signal Transduction / drug effects
T-Lymphocyte Subsets / drug effects
T-Lymphocyte Subsets / immunology
T-Lymphocyte Subsets / metabolism
Tea / chemistry*
Xenograft Model Antitumor Assays
|
| IF |
3.06
|
| 引用数 |
21
|
| リソース情報 |
| ヒト・動物細胞 |
Lu99(RCB1900) |
