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

被引:18
作者
Kim, Ji Hye [1 ]
Kim, Young Soo [1 ]
Kim, Tae In [1 ]
Li, Wei [1 ]
Mun, Jeong-Geon [2 ]
Jeon, Hee Dong [2 ]
Kee, Ji-Ye [2 ]
Choi, Jang-Gi [1 ]
Chung, Hwan-Suck [1 ]
机构
[1] Korea Inst Oriental Med KIOM, Korean Med KM Applicat Ctr, Daegu 41062, South Korea
[2] Wonkwang Univ, Dept Oriental Pharm, Coll Pharm, Wonkwang Oriental Med Res Inst, 460 Iksandae Ro, Iksan 54538, Jeonbuk, South Korea
基金
新加坡国家研究基金会;
关键词
black raspberry; ellagic acid; antitumor immunity; T cell function; programmed cell death protein 1; programmed death-ligand 1; COLON-CANCER; APOPTOSIS;
D O I
10.3390/foods9111590
中图分类号
TS2 [食品工业];
学科分类号
0832 ;
摘要
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.
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页数:13
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