Cargando…

Unripe Black Raspberry (Rubus coreanus Miquel) Extract and Its Constitute, Ellagic Acid Induces T Cell Activation and Antitumor Immunity by Blocking PD-1/PD-L1 Interaction

Rubus coreanus Miquel (R. coreanus) is a unripen fruit of black raspberry native to eastern Asia. It is used as traditional oriental medicine and supplementary foods for centuries. Previous studies have shown that the R. coreanus extract (RCE) and its main constitute ellagic acid possess diverse bio...

Descripción completa

Detalles Bibliográficos
Autores principales: Kim, Ji Hye, Kim, Young Soo, Kim, Tae In, Li, Wei, Mun, Jeong-Geon, Jeon, Hee Dong, Kee, Ji-Ye, Choi, Jang-Gi, Chung, Hwan-Suck
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693366/
https://www.ncbi.nlm.nih.gov/pubmed/33147777
http://dx.doi.org/10.3390/foods9111590
_version_ 1783614727500333056
author Kim, Ji Hye
Kim, Young Soo
Kim, Tae In
Li, Wei
Mun, Jeong-Geon
Jeon, Hee Dong
Kee, Ji-Ye
Choi, Jang-Gi
Chung, Hwan-Suck
author_facet Kim, Ji Hye
Kim, Young Soo
Kim, Tae In
Li, Wei
Mun, Jeong-Geon
Jeon, Hee Dong
Kee, Ji-Ye
Choi, Jang-Gi
Chung, Hwan-Suck
author_sort Kim, Ji Hye
collection PubMed
description Rubus coreanus Miquel (R. coreanus) is a unripen fruit of black raspberry native to eastern Asia. It is used as traditional oriental medicine and supplementary foods for centuries. Previous studies have shown that the R. coreanus extract (RCE) and its main constitute ellagic acid possess diverse biological activities. However, the effects of RCE on antitumor immunity and T cell function were not fully understood. The present study describes the anti-tumor effect of RCE in humanized PD-1 mice by blocking PD-1/PD-L1 interaction. Competitive enzyme-linked immunosorbent assay (ELISA) and pull down assay were performed to elucidate the binding properties of RCE in vitro. Cellular PD-1/PD-L1 blockade activities were measured by T cell receptor (TCR)-induced nuclear factor of activated T cells-luciferase activity in co-cultured cell models with PD-1/NFAT Jurkat and PD-L1/aAPC CHO-K1 cells. The in vivo efficacy of RCE was confirmed in humanized PD-1 mice bearing MC38 colorectal tumor. RCE and ellagic acid dose-dependently block the binding of PD-1 to PD-L1. Moreover, oral administration of RCE showed the potent anti-tumor activity similar to anti-PD-1 antibody. The present study suggests that RCE possesses potent anti-tumor effect via PD-1/PD-L1 blockade, and ellagic acid is the main compound in RCE. Thus, we provide new aspects of RCE as an immunotherapeutic agent.
format Online
Article
Text
id pubmed-7693366
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-76933662020-11-28 Unripe Black Raspberry (Rubus coreanus Miquel) Extract and Its Constitute, Ellagic Acid Induces T Cell Activation and Antitumor Immunity by Blocking PD-1/PD-L1 Interaction Kim, Ji Hye Kim, Young Soo Kim, Tae In Li, Wei Mun, Jeong-Geon Jeon, Hee Dong Kee, Ji-Ye Choi, Jang-Gi Chung, Hwan-Suck Foods Article Rubus coreanus Miquel (R. coreanus) is a unripen fruit of black raspberry native to eastern Asia. It is used as traditional oriental medicine and supplementary foods for centuries. Previous studies have shown that the R. coreanus extract (RCE) and its main constitute ellagic acid possess diverse biological activities. However, the effects of RCE on antitumor immunity and T cell function were not fully understood. The present study describes the anti-tumor effect of RCE in humanized PD-1 mice by blocking PD-1/PD-L1 interaction. Competitive enzyme-linked immunosorbent assay (ELISA) and pull down assay were performed to elucidate the binding properties of RCE in vitro. Cellular PD-1/PD-L1 blockade activities were measured by T cell receptor (TCR)-induced nuclear factor of activated T cells-luciferase activity in co-cultured cell models with PD-1/NFAT Jurkat and PD-L1/aAPC CHO-K1 cells. The in vivo efficacy of RCE was confirmed in humanized PD-1 mice bearing MC38 colorectal tumor. RCE and ellagic acid dose-dependently block the binding of PD-1 to PD-L1. Moreover, oral administration of RCE showed the potent anti-tumor activity similar to anti-PD-1 antibody. The present study suggests that RCE possesses potent anti-tumor effect via PD-1/PD-L1 blockade, and ellagic acid is the main compound in RCE. Thus, we provide new aspects of RCE as an immunotherapeutic agent. MDPI 2020-11-02 /pmc/articles/PMC7693366/ /pubmed/33147777 http://dx.doi.org/10.3390/foods9111590 Text en © 2020 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
Kim, Ji Hye
Kim, Young Soo
Kim, Tae In
Li, Wei
Mun, Jeong-Geon
Jeon, Hee Dong
Kee, Ji-Ye
Choi, Jang-Gi
Chung, Hwan-Suck
Unripe Black Raspberry (Rubus coreanus Miquel) Extract and Its Constitute, Ellagic Acid Induces T Cell Activation and Antitumor Immunity by Blocking PD-1/PD-L1 Interaction
title Unripe Black Raspberry (Rubus coreanus Miquel) Extract and Its Constitute, Ellagic Acid Induces T Cell Activation and Antitumor Immunity by Blocking PD-1/PD-L1 Interaction
title_full Unripe Black Raspberry (Rubus coreanus Miquel) Extract and Its Constitute, Ellagic Acid Induces T Cell Activation and Antitumor Immunity by Blocking PD-1/PD-L1 Interaction
title_fullStr Unripe Black Raspberry (Rubus coreanus Miquel) Extract and Its Constitute, Ellagic Acid Induces T Cell Activation and Antitumor Immunity by Blocking PD-1/PD-L1 Interaction
title_full_unstemmed Unripe Black Raspberry (Rubus coreanus Miquel) Extract and Its Constitute, Ellagic Acid Induces T Cell Activation and Antitumor Immunity by Blocking PD-1/PD-L1 Interaction
title_short Unripe Black Raspberry (Rubus coreanus Miquel) Extract and Its Constitute, Ellagic Acid Induces T Cell Activation and Antitumor Immunity by Blocking PD-1/PD-L1 Interaction
title_sort unripe black raspberry (rubus coreanus miquel) extract and its constitute, ellagic acid induces t cell activation and antitumor immunity by blocking pd-1/pd-l1 interaction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693366/
https://www.ncbi.nlm.nih.gov/pubmed/33147777
http://dx.doi.org/10.3390/foods9111590
work_keys_str_mv AT kimjihye unripeblackraspberryrubuscoreanusmiquelextractanditsconstituteellagicacidinducestcellactivationandantitumorimmunitybyblockingpd1pdl1interaction
AT kimyoungsoo unripeblackraspberryrubuscoreanusmiquelextractanditsconstituteellagicacidinducestcellactivationandantitumorimmunitybyblockingpd1pdl1interaction
AT kimtaein unripeblackraspberryrubuscoreanusmiquelextractanditsconstituteellagicacidinducestcellactivationandantitumorimmunitybyblockingpd1pdl1interaction
AT liwei unripeblackraspberryrubuscoreanusmiquelextractanditsconstituteellagicacidinducestcellactivationandantitumorimmunitybyblockingpd1pdl1interaction
AT munjeonggeon unripeblackraspberryrubuscoreanusmiquelextractanditsconstituteellagicacidinducestcellactivationandantitumorimmunitybyblockingpd1pdl1interaction
AT jeonheedong unripeblackraspberryrubuscoreanusmiquelextractanditsconstituteellagicacidinducestcellactivationandantitumorimmunitybyblockingpd1pdl1interaction
AT keejiye unripeblackraspberryrubuscoreanusmiquelextractanditsconstituteellagicacidinducestcellactivationandantitumorimmunitybyblockingpd1pdl1interaction
AT choijanggi unripeblackraspberryrubuscoreanusmiquelextractanditsconstituteellagicacidinducestcellactivationandantitumorimmunitybyblockingpd1pdl1interaction
AT chunghwansuck unripeblackraspberryrubuscoreanusmiquelextractanditsconstituteellagicacidinducestcellactivationandantitumorimmunitybyblockingpd1pdl1interaction