Unripe Black Raspberry (<i>Rubus coreanus</i> Miquel) Extract and Its Constitute, Ellagic Acid Induces T Cell Activation and Antitumor Immunity by Blocking PD-1/PD-L1 Interaction
<i>Rubus coreanus</i> Miquel (<i>R. coreanus</i>) 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 <i>R. coreanus</i> extract (RCE)...
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MDPI AG
2020-11-01
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| Series: | Foods |
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| Online Access: | https://www.mdpi.com/2304-8158/9/11/1590 |
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| author | Ji Hye Kim Young Soo Kim Tae In Kim Wei Li Jeong-Geon Mun Hee Dong Jeon Ji-Ye Kee Jang-Gi Choi Hwan-Suck Chung |
| author_facet | Ji Hye Kim Young Soo Kim Tae In Kim Wei Li Jeong-Geon Mun Hee Dong Jeon Ji-Ye Kee Jang-Gi Choi Hwan-Suck Chung |
| author_sort | Ji Hye Kim |
| collection | DOAJ |
| description | <i>Rubus coreanus</i> Miquel (<i>R. coreanus</i>) 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 <i>R. coreanus</i> 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. |
| first_indexed | 2024-03-10T15:08:50Z |
| format | Article |
| id | doaj.art-3a41fe767c1a450ba7ed673434eabc19 |
| institution | Directory Open Access Journal |
| issn | 2304-8158 |
| language | English |
| last_indexed | 2024-03-10T15:08:50Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Foods |
| spelling | doaj.art-3a41fe767c1a450ba7ed673434eabc192023-11-20T19:31:08ZengMDPI AGFoods2304-81582020-11-01911159010.3390/foods9111590Unripe Black Raspberry (<i>Rubus coreanus</i> Miquel) Extract and Its Constitute, Ellagic Acid Induces T Cell Activation and Antitumor Immunity by Blocking PD-1/PD-L1 InteractionJi Hye Kim0Young Soo Kim1Tae In Kim2Wei Li3Jeong-Geon Mun4Hee Dong Jeon5Ji-Ye Kee6Jang-Gi Choi7Hwan-Suck Chung8Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Dong-gu, Daegu 41062, KoreaKorean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Dong-gu, Daegu 41062, KoreaKorean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Dong-gu, Daegu 41062, KoreaKorean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Dong-gu, Daegu 41062, KoreaDepartment of Oriental Pharmacy, College of Pharmacy, Wonkwang-Oriental Medicines Research Institute, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, KoreaDepartment of Oriental Pharmacy, College of Pharmacy, Wonkwang-Oriental Medicines Research Institute, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, KoreaDepartment of Oriental Pharmacy, College of Pharmacy, Wonkwang-Oriental Medicines Research Institute, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, KoreaKorean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Dong-gu, Daegu 41062, KoreaKorean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Dong-gu, Daegu 41062, Korea<i>Rubus coreanus</i> Miquel (<i>R. coreanus</i>) 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 <i>R. coreanus</i> 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.https://www.mdpi.com/2304-8158/9/11/1590black raspberryellagic acidantitumor immunityT cell functionprogrammed cell death protein 1programmed death-ligand 1 |
| spellingShingle | Ji Hye Kim Young Soo Kim Tae In Kim Wei Li Jeong-Geon Mun Hee Dong Jeon Ji-Ye Kee Jang-Gi Choi Hwan-Suck Chung Unripe Black Raspberry (<i>Rubus coreanus</i> Miquel) Extract and Its Constitute, Ellagic Acid Induces T Cell Activation and Antitumor Immunity by Blocking PD-1/PD-L1 Interaction Foods black raspberry ellagic acid antitumor immunity T cell function programmed cell death protein 1 programmed death-ligand 1 |
| title | Unripe Black Raspberry (<i>Rubus coreanus</i> 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 (<i>Rubus coreanus</i> 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 (<i>Rubus coreanus</i> 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 (<i>Rubus coreanus</i> 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 (<i>Rubus coreanus</i> 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 i rubus coreanus i miquel extract and its constitute ellagic acid induces t cell activation and antitumor immunity by blocking pd 1 pd l1 interaction |
| topic | black raspberry ellagic acid antitumor immunity T cell function programmed cell death protein 1 programmed death-ligand 1 |
| url | https://www.mdpi.com/2304-8158/9/11/1590 |
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