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A novel cell-based screen identifies chemical entities that reverse the immune-escape phenotype of metastatic tumours
Genetic and epigenetic events have been implicated in the downregulation of the cellular antigen processing and presentation machinery (APM), which in turn, has been associated with cancer evasion of the immune system. When these essential components are lacking, cancers develop the ability to subve...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10225555/ https://www.ncbi.nlm.nih.gov/pubmed/37256225 http://dx.doi.org/10.3389/fphar.2023.1119607 |
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author | Nohara, Lilian L. Ellis, Samantha L. S. Dreier, Carola Dada, Sarah Saranchova, Iryna Choi, Kyong Bok Munro, Lonna Pfeifer, Cheryl G. Al Haddad, Eliana Coyle, Krysta M. Morrice, Jessica R. Shim, Daniel Joo Sung Ahn, Paul De Voogd, Nicole Williams, David E. Cheng, Ping Garrovillas, Emmanuel Andersen, Raymond J. Jefferies, Wilfred A. |
author_facet | Nohara, Lilian L. Ellis, Samantha L. S. Dreier, Carola Dada, Sarah Saranchova, Iryna Choi, Kyong Bok Munro, Lonna Pfeifer, Cheryl G. Al Haddad, Eliana Coyle, Krysta M. Morrice, Jessica R. Shim, Daniel Joo Sung Ahn, Paul De Voogd, Nicole Williams, David E. Cheng, Ping Garrovillas, Emmanuel Andersen, Raymond J. Jefferies, Wilfred A. |
author_sort | Nohara, Lilian L. |
collection | PubMed |
description | Genetic and epigenetic events have been implicated in the downregulation of the cellular antigen processing and presentation machinery (APM), which in turn, has been associated with cancer evasion of the immune system. When these essential components are lacking, cancers develop the ability to subvert host immune surveillance allowing cancer cells to become invisible to the immune system and, in turn, promote cancer metastasis. Here we describe and validate the first high-throughput cell-based screening assay to identify chemical extracts and unique chemical entities that reverse the downregulation of APM components in cell lines derived from metastatic tumours. Through the screening of a library of 480 marine invertebrate extracts followed by bioassay-guided fractionation, curcuphenol, a common sesquiterpene phenol derived from turmeric, was identified as the active compound of one of the extracts. We demonstrate that curcuphenol induces the expression of the APM components, TAP-1 and MHC-I molecules, in cell lines derived from both metastatic prostate and lung carcinomas. Turmeric and curcumins that contain curcuphenol have long been utilized not only as a spice in the preparation of food, but also in traditional medicines for treating cancers. The remarkable discovery that a common component of spices can increase the expression of APM components in metastatic tumour cells and, therefore reverse immune-escape mechanisms, provides a rationale for the development of foods and advanced nutraceuticals as therapeutic candidates for harnessing the power of the immune system to recognize and destroy metastatic cancers. |
format | Online Article Text |
id | pubmed-10225555 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-102255552023-05-30 A novel cell-based screen identifies chemical entities that reverse the immune-escape phenotype of metastatic tumours Nohara, Lilian L. Ellis, Samantha L. S. Dreier, Carola Dada, Sarah Saranchova, Iryna Choi, Kyong Bok Munro, Lonna Pfeifer, Cheryl G. Al Haddad, Eliana Coyle, Krysta M. Morrice, Jessica R. Shim, Daniel Joo Sung Ahn, Paul De Voogd, Nicole Williams, David E. Cheng, Ping Garrovillas, Emmanuel Andersen, Raymond J. Jefferies, Wilfred A. Front Pharmacol Pharmacology Genetic and epigenetic events have been implicated in the downregulation of the cellular antigen processing and presentation machinery (APM), which in turn, has been associated with cancer evasion of the immune system. When these essential components are lacking, cancers develop the ability to subvert host immune surveillance allowing cancer cells to become invisible to the immune system and, in turn, promote cancer metastasis. Here we describe and validate the first high-throughput cell-based screening assay to identify chemical extracts and unique chemical entities that reverse the downregulation of APM components in cell lines derived from metastatic tumours. Through the screening of a library of 480 marine invertebrate extracts followed by bioassay-guided fractionation, curcuphenol, a common sesquiterpene phenol derived from turmeric, was identified as the active compound of one of the extracts. We demonstrate that curcuphenol induces the expression of the APM components, TAP-1 and MHC-I molecules, in cell lines derived from both metastatic prostate and lung carcinomas. Turmeric and curcumins that contain curcuphenol have long been utilized not only as a spice in the preparation of food, but also in traditional medicines for treating cancers. The remarkable discovery that a common component of spices can increase the expression of APM components in metastatic tumour cells and, therefore reverse immune-escape mechanisms, provides a rationale for the development of foods and advanced nutraceuticals as therapeutic candidates for harnessing the power of the immune system to recognize and destroy metastatic cancers. Frontiers Media S.A. 2023-05-15 /pmc/articles/PMC10225555/ /pubmed/37256225 http://dx.doi.org/10.3389/fphar.2023.1119607 Text en Copyright © 2023 Nohara, Ellis, Dreier, Dada, Saranchova, Choi, Munro, Pfeifer, Al Haddad, Coyle, Morrice, Shim, Ahn, De Voogd, Williams, Cheng, Garrovillas, Andersen and Jefferies. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Nohara, Lilian L. Ellis, Samantha L. S. Dreier, Carola Dada, Sarah Saranchova, Iryna Choi, Kyong Bok Munro, Lonna Pfeifer, Cheryl G. Al Haddad, Eliana Coyle, Krysta M. Morrice, Jessica R. Shim, Daniel Joo Sung Ahn, Paul De Voogd, Nicole Williams, David E. Cheng, Ping Garrovillas, Emmanuel Andersen, Raymond J. Jefferies, Wilfred A. A novel cell-based screen identifies chemical entities that reverse the immune-escape phenotype of metastatic tumours |
title | A novel cell-based screen identifies chemical entities that reverse the immune-escape phenotype of metastatic tumours |
title_full | A novel cell-based screen identifies chemical entities that reverse the immune-escape phenotype of metastatic tumours |
title_fullStr | A novel cell-based screen identifies chemical entities that reverse the immune-escape phenotype of metastatic tumours |
title_full_unstemmed | A novel cell-based screen identifies chemical entities that reverse the immune-escape phenotype of metastatic tumours |
title_short | A novel cell-based screen identifies chemical entities that reverse the immune-escape phenotype of metastatic tumours |
title_sort | novel cell-based screen identifies chemical entities that reverse the immune-escape phenotype of metastatic tumours |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10225555/ https://www.ncbi.nlm.nih.gov/pubmed/37256225 http://dx.doi.org/10.3389/fphar.2023.1119607 |
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