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Kaempferol and Its Glycoside, Kaempferol 7-O-rhamnoside, Inhibit PD-1/PD-L1 Interaction In Vitro
Kaempferol (KO) and kaempferol 7-O-rhamnoside (KR) are natural products from various oriental herbs such as Geranii Herba. Previous studies have reported some biological activities of KO and KR; however, their effects on PD-1/PD-L1 interaction have not been reported yet. To elucidate their inhibitor...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247329/ https://www.ncbi.nlm.nih.gov/pubmed/32375257 http://dx.doi.org/10.3390/ijms21093239 |
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author | Kim, Ji Hye Kim, Young Soo Choi, Jang-Gi Li, Wei Lee, Eun Jin Park, Jin-Wan Song, Jaeyoung Chung, Hwan-Suck |
author_facet | Kim, Ji Hye Kim, Young Soo Choi, Jang-Gi Li, Wei Lee, Eun Jin Park, Jin-Wan Song, Jaeyoung Chung, Hwan-Suck |
author_sort | Kim, Ji Hye |
collection | PubMed |
description | Kaempferol (KO) and kaempferol 7-O-rhamnoside (KR) are natural products from various oriental herbs such as Geranii Herba. Previous studies have reported some biological activities of KO and KR; however, their effects on PD-1/PD-L1 interaction have not been reported yet. To elucidate their inhibitory activities on PD-1/PD-L1 protein–protein interaction (PPI), biochemical assays including competitive ELISA and biolayer interferometry (BLI) systems were performed. Cellular PD-1/PD-L1 blocking activity was measured in a co-culture system with PD-1 Jurkat and PD-L1/aAPC CHO-K1 cells by T-cell receptor (TCR) activation-induced nuclear factor of activated T cells (NFAT)-luciferase reporter assay. The detailed binding mode of action was simulated by an in silico docking study and pharmacophore analysis. Competitive ELISA revealed that KO and its glycoside KR significantly inhibited PD-1/PD-L1 interaction. Cellular PD-1/PD-L1 blocking activity was monitored by KO and KR at non-cytotoxic concentration. Surface plasmon resonance (SPR) and biolayer interferometry (BLI) analysis suggested the binding affinity and direct inhibition of KR against PD-1/PD-L1. An in silico docking simulation determined the detailed mode of binding of KR to PD-1/PD-L1. Collectively, these results suggest that KR could be developed as a potent small molecule inhibitor for PD-1/PD-L1 blockade. |
format | Online Article Text |
id | pubmed-7247329 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72473292020-06-10 Kaempferol and Its Glycoside, Kaempferol 7-O-rhamnoside, Inhibit PD-1/PD-L1 Interaction In Vitro Kim, Ji Hye Kim, Young Soo Choi, Jang-Gi Li, Wei Lee, Eun Jin Park, Jin-Wan Song, Jaeyoung Chung, Hwan-Suck Int J Mol Sci Article Kaempferol (KO) and kaempferol 7-O-rhamnoside (KR) are natural products from various oriental herbs such as Geranii Herba. Previous studies have reported some biological activities of KO and KR; however, their effects on PD-1/PD-L1 interaction have not been reported yet. To elucidate their inhibitory activities on PD-1/PD-L1 protein–protein interaction (PPI), biochemical assays including competitive ELISA and biolayer interferometry (BLI) systems were performed. Cellular PD-1/PD-L1 blocking activity was measured in a co-culture system with PD-1 Jurkat and PD-L1/aAPC CHO-K1 cells by T-cell receptor (TCR) activation-induced nuclear factor of activated T cells (NFAT)-luciferase reporter assay. The detailed binding mode of action was simulated by an in silico docking study and pharmacophore analysis. Competitive ELISA revealed that KO and its glycoside KR significantly inhibited PD-1/PD-L1 interaction. Cellular PD-1/PD-L1 blocking activity was monitored by KO and KR at non-cytotoxic concentration. Surface plasmon resonance (SPR) and biolayer interferometry (BLI) analysis suggested the binding affinity and direct inhibition of KR against PD-1/PD-L1. An in silico docking simulation determined the detailed mode of binding of KR to PD-1/PD-L1. Collectively, these results suggest that KR could be developed as a potent small molecule inhibitor for PD-1/PD-L1 blockade. MDPI 2020-05-03 /pmc/articles/PMC7247329/ /pubmed/32375257 http://dx.doi.org/10.3390/ijms21093239 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 Choi, Jang-Gi Li, Wei Lee, Eun Jin Park, Jin-Wan Song, Jaeyoung Chung, Hwan-Suck Kaempferol and Its Glycoside, Kaempferol 7-O-rhamnoside, Inhibit PD-1/PD-L1 Interaction In Vitro |
title | Kaempferol and Its Glycoside, Kaempferol 7-O-rhamnoside, Inhibit PD-1/PD-L1 Interaction In Vitro |
title_full | Kaempferol and Its Glycoside, Kaempferol 7-O-rhamnoside, Inhibit PD-1/PD-L1 Interaction In Vitro |
title_fullStr | Kaempferol and Its Glycoside, Kaempferol 7-O-rhamnoside, Inhibit PD-1/PD-L1 Interaction In Vitro |
title_full_unstemmed | Kaempferol and Its Glycoside, Kaempferol 7-O-rhamnoside, Inhibit PD-1/PD-L1 Interaction In Vitro |
title_short | Kaempferol and Its Glycoside, Kaempferol 7-O-rhamnoside, Inhibit PD-1/PD-L1 Interaction In Vitro |
title_sort | kaempferol and its glycoside, kaempferol 7-o-rhamnoside, inhibit pd-1/pd-l1 interaction in vitro |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247329/ https://www.ncbi.nlm.nih.gov/pubmed/32375257 http://dx.doi.org/10.3390/ijms21093239 |
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