QPH-FR: A Novel Quinoa Peptide Enhances Chemosensitivity by Targeting Leucine-Rich Repeat-Containing G Protein-Coupled Receptor 5 in Colorectal Cancer,Journal of Agricultural and Food Chemistry

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QPH-FR: A Novel Quinoa Peptide Enhances Chemosensitivity by Targeting Leucine-Rich Repeat-Containing G Protein-Coupled Receptor 5 in Colorectal Cancer
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2024-07-24 , DOI: 10.1021/acs.jafc.4c03761
Jinmiao Tian ₁ , Lichao Zhang ₂ , Xiaoqin La ₂ , Yuxuan An ₁ , Xiaxia Fan ₁ , Zhuoyu Li ₁

Affiliation

Chemoresistance is one of the difficulties in the treatment of colorectal cancer (CRC), and the enhanced stemness of tumor cells is the underlying contributing factor. Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a classical marker of CRC stem cells and can be an important potential target for CRC chemotherapy. Quinoa, a protein-rich plant, offers potential as a source of high-quality active peptides. Novelly, the study obtained quinoa protein hydrolysate (QPH) from whole quinoa grains by simulated digestion. In vivo experiments revealed that the tumor volume in the 5-FU+QPH group decreased from 145.90 ± 13.35 to 94.49 ± 13.05 mm³ in the 5-FU group, suggesting that QPH enhances the chemosensitivity of CRC. Further, the most effective peptide QPH-FR from 631 peptides in QPH was screened by activity prediction, molecular docking, and experimental validation. Mechanistically, QPH-FR competitively suppressed the formation of the LGR5/RSPO1 complex by binding to LGR5, causing RNF43/ZNRF3 to ubiquitinate the FZD receptor, thereby suppressing the Wnt/β-catenin signaling pathway and exerting stemness inhibition. In summary, the study proposes that a novel peptide QPH-FR from quinoa elucidates the mechanism by which QPH-FR targets LGR5 to enhance chemosensitivity, providing theoretical support for the development of chemotherapeutic adjuvant drugs based on plant peptides.

中文翻译：

QPH-FR：一种新型藜麦肽通过靶向富含亮氨酸重复序列的 G 蛋白偶联受体 5 来增强结直肠癌的化疗敏感性

化疗耐药是结直肠癌（CRC）治疗的难点之一，肿瘤细胞干性增强是其根本原因。富含亮氨酸重复序列的 G 蛋白偶联受体 5 (LGR5) 是 CRC 干细胞的经典标志物，可以成为 CRC 化疗的重要潜在靶点。藜麦是一种富含蛋白质的植物，具有作为优质活性肽来源的潜力。新颖的是，该研究通过模拟消化从全藜麦谷物中获得了藜麦蛋白水解物（QPH）。体内实验显示，5-FU+QPH组的肿瘤体积从145.90±13.35减小至5-FU组的94.49±13.05 mm ³ ，表明QPH增强了CRC的化疗敏感性。进一步通过活性预测、分子对接和实验验证，从QPH中的631个肽中筛选出最有效的肽QPH-FR。机制上，QPH-FR通过与LGR5结合，竞争性抑制LGR5/RSPO1复合物的形成，导致RNF43/ZNRF3泛素化FZD受体，从而抑制Wnt/β-catenin信号通路，发挥干性抑制作用。综上所述，该研究提出来自藜麦的一种新型肽QPH-FR阐明了QPH-FR靶向LGR5增强化疗敏感性的机制，为基于植物肽的化疗辅助药物的开发提供理论支持。

更新日期：2024-07-24

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