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Article

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

by
Ji Hye Kim
1,
Young Soo Kim
1,
Tae In Kim
1,
Wei Li
1,
Jeong-Geon Mun
2,
Hee Dong Jeon
2,
Ji-Ye Kee
2,
Jang-Gi Choi
1,* and
Hwan-Suck Chung
1,*
1
Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Dong-gu, Daegu 41062, Korea
2
Department of Oriental Pharmacy, College of Pharmacy, Wonkwang-Oriental Medicines Research Institute, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, Korea
*
Authors to whom correspondence should be addressed.
Foods 2020, 9(11), 1590; https://doi.org/10.3390/foods9111590
Submission received: 25 September 2020 / Revised: 27 October 2020 / Accepted: 30 October 2020 / Published: 2 November 2020
(This article belongs to the Special Issue Dietary Bioactive Compound and Health)
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Abstract

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.
Keywords: black raspberry; ellagic acid; antitumor immunity; T cell function; programmed cell death protein 1; programmed death-ligand 1 black raspberry; ellagic acid; antitumor immunity; T cell function; programmed cell death protein 1; programmed death-ligand 1
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MDPI and ACS Style

Kim, J.H.; Kim, Y.S.; Kim, T.I.; Li, W.; Mun, J.-G.; Jeon, H.D.; Kee, J.-Y.; Choi, J.-G.; Chung, H.-S. 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. Foods 2020, 9, 1590. https://doi.org/10.3390/foods9111590

AMA Style

Kim JH, Kim YS, Kim TI, Li W, Mun J-G, Jeon HD, Kee J-Y, Choi J-G, Chung H-S. 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. Foods. 2020; 9(11):1590. https://doi.org/10.3390/foods9111590

Chicago/Turabian Style

Kim, Ji Hye, Young Soo Kim, Tae In Kim, Wei Li, Jeong-Geon Mun, Hee Dong Jeon, Ji-Ye Kee, Jang-Gi Choi, and Hwan-Suck Chung. 2020. "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" Foods 9, no. 11: 1590. https://doi.org/10.3390/foods9111590

APA Style

Kim, J. H., Kim, Y. S., Kim, T. I., Li, W., Mun, J.-G., Jeon, H. D., Kee, J.-Y., Choi, J.-G., & Chung, H.-S. (2020). 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. Foods, 9(11), 1590. https://doi.org/10.3390/foods9111590

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