Curcuphenol possesses an unusual histone deacetylase enhancing activity that counters immune escape in metastatic tumours

Curcuphenol, a common component of the culinary spices, naturally found in marine invertebrates and plants, has been identified as a novel candidate for reversing immune escape by restoring expression of the antigen presentation machinery (APM) in invasive cancers, thereby resurrecting the immune re...

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Published inFrontiers in pharmacology Vol. 14; p. 1119620
Main Authors Ellis, Samantha L. S., Dada, Sarah, Nohara, Lilian L., Saranchova, Iryna, Munro, Lonna, Pfeifer, Cheryl G., Eyford, Brett A., Morova, Tunc, Williams, David E., Cheng, Ping, Lack, Nathan A., Andersen, Raymond J., Jefferies, Wilfred A.
Format Journal Article
LanguageEnglish
Published Frontiers Media S.A 10.08.2023
Subjects
antigen processing machinery
curcuphenol
epigenetic modification
HDAC
histone deacetylase activity
major histocompatibility complex class I
Pharmacology
Online AccessGet full text
ISSN1663-9812
1663-9812
DOI10.3389/fphar.2023.1119620

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Abstract Curcuphenol, a common component of the culinary spices, naturally found in marine invertebrates and plants, has been identified as a novel candidate for reversing immune escape by restoring expression of the antigen presentation machinery (APM) in invasive cancers, thereby resurrecting the immune recognition of metastatic tumours. Two synthetic curcuphenol analogues, were prepared by informed design that demonstrated consistent induction of APM expression in metastatic prostate and lung carcinoma cells. Both analogues were subsequently found to possess a previously undescribed histone deacetylase (HDAC)-enhancing activity. Remarkably, the H3K27ac ChIPseq analysis of curcuphenol-treated cells reveals that the induced epigenomic marks closely resemble the changes in genome-wide pattern observed with interferon-γ, a cytokine instrumental for orchestrating innate and adaptive immunity. These observations link dietary components to modifying epigenetic programs that modulate gene expression guiding poised immunity.
AbstractList Curcuphenol, a common component of the culinary spices, naturally found in marine invertebrates and plants, has been identified as a novel candidate for reversing immune escape by restoring expression of the antigen presentation machinery (APM) in invasive cancers, thereby resurrecting the immune recognition of metastatic tumours. Two synthetic curcuphenol analogues, were prepared by informed design that demonstrated consistent induction of APM expression in metastatic prostate and lung carcinoma cells. Both analogues were subsequently found to possess a previously undescribed histone deacetylase (HDAC)-enhancing activity. Remarkably, the H3K27ac ChIPseq analysis of curcuphenol-treated cells reveals that the induced epigenomic marks closely resemble the changes in genome-wide pattern observed with interferon-γ, a cytokine instrumental for orchestrating innate and adaptive immunity. These observations link dietary components to modifying epigenetic programs that modulate gene expression guiding poised immunity.
Curcuphenol, a common component of the culinary spices, naturally found in marine invertebrates and plants, has been identified as a novel candidate for reversing immune escape by restoring expression of the antigen presentation machinery (APM) in invasive cancers, thereby resurrecting the immune recognition of metastatic tumours. Two synthetic curcuphenol analogues, were prepared by informed design that demonstrated consistent induction of APM expression in metastatic prostate and lung carcinoma cells. Both analogues were subsequently found to possess a previously undescribed histone deacetylase (HDAC)-enhancing activity. Remarkably, the H3K27ac ChIPseq analysis of curcuphenol-treated cells reveals that the induced epigenomic marks closely resemble the changes in genome-wide pattern observed with interferon-γ, a cytokine instrumental for orchestrating innate and adaptive immunity. These observations link dietary components to modifying epigenetic programs that modulate gene expression guiding poised immunity.Curcuphenol, a common component of the culinary spices, naturally found in marine invertebrates and plants, has been identified as a novel candidate for reversing immune escape by restoring expression of the antigen presentation machinery (APM) in invasive cancers, thereby resurrecting the immune recognition of metastatic tumours. Two synthetic curcuphenol analogues, were prepared by informed design that demonstrated consistent induction of APM expression in metastatic prostate and lung carcinoma cells. Both analogues were subsequently found to possess a previously undescribed histone deacetylase (HDAC)-enhancing activity. Remarkably, the H3K27ac ChIPseq analysis of curcuphenol-treated cells reveals that the induced epigenomic marks closely resemble the changes in genome-wide pattern observed with interferon-γ, a cytokine instrumental for orchestrating innate and adaptive immunity. These observations link dietary components to modifying epigenetic programs that modulate gene expression guiding poised immunity.
Author Pfeifer, Cheryl G.
Andersen, Raymond J.
Eyford, Brett A.
Jefferies, Wilfred A.
Nohara, Lilian L.
Munro, Lonna
Cheng, Ping
Dada, Sarah
Saranchova, Iryna
Morova, Tunc
Ellis, Samantha L. S.
Williams, David E.
Lack, Nathan A.
AuthorAffiliation 8 School of Medicine , Koç University , Istanbul , Türkiye
3 The Djavad Mowafaghian Centre for Brain Health , University of British Columbia , Vancouver , BC , Canada
7 Departments of Chemistry and Earth Ocean, and Atmospheric Sciences , University of British Columbia , Vancouver , BC , Canada
5 Vancouver Prostate Centre , Vancouver Coastal Health Research Institute , Vancouver , BC , Canada
4 Department of Microbiology and Immunology , University of British Columbia , Vancouver , BC , Canada
1 Michael Smith Laboratories , University of British Columbia , Vancouver , BC , Canada
6 Departments of Medical Genetics, Zoology, and Urologic Sciences , University of British Columbia , Vancouver , BC , Canada
2 Centre for Blood Research , University of British Columbia , Vancouver , BC , Canada
AuthorAffiliation_xml – name: 1 Michael Smith Laboratories , University of British Columbia , Vancouver , BC , Canada
– name: 4 Department of Microbiology and Immunology , University of British Columbia , Vancouver , BC , Canada
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– name: 8 School of Medicine , Koç University , Istanbul , Türkiye
– name: 2 Centre for Blood Research , University of British Columbia , Vancouver , BC , Canada
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Copyright Copyright © 2023 Ellis, Dada, Nohara, Saranchova, Munro, Pfeifer, Eyford, Morova, Williams, Cheng, Lack, Andersen and Jefferies.
Copyright © 2023 Ellis, Dada, Nohara, Saranchova, Munro, Pfeifer, Eyford, Morova, Williams, Cheng, Lack, Andersen and Jefferies. 2023 Ellis, Dada, Nohara, Saranchova, Munro, Pfeifer, Eyford, Morova, Williams, Cheng, Lack, Andersen and Jefferies
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Edited by: Rakesh Naidu, Monash University Malaysia, Malaysia
Reviewed by: Joko Tri Wibowo, National Research and Innovation Agency (BRIN), Indonesia
Belgin Sever, Anadolu University, Türkiye
These authors share first authorship
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Snippet Curcuphenol, a common component of the culinary spices, naturally found in marine invertebrates and plants, has been identified as a novel candidate for...
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SubjectTerms antigen processing machinery
curcuphenol
epigenetic modification
HDAC
histone deacetylase activity
major histocompatibility complex class I
Pharmacology
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Title Curcuphenol possesses an unusual histone deacetylase enhancing activity that counters immune escape in metastatic tumours
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https://pubmed.ncbi.nlm.nih.gov/PMC10449465
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