Frontiers in Pharmacology (Aug 2023)
Curcuphenol possesses an unusual histone deacetylase enhancing activity that counters immune escape in metastatic tumours
- Samantha L. S. Ellis,
- Samantha L. S. Ellis,
- Samantha L. S. Ellis,
- Samantha L. S. Ellis,
- Sarah Dada,
- Sarah Dada,
- Sarah Dada,
- Sarah Dada,
- Sarah Dada,
- Sarah Dada,
- Lilian L. Nohara,
- Lilian L. Nohara,
- Lilian L. Nohara,
- Iryna Saranchova,
- Iryna Saranchova,
- Iryna Saranchova,
- Iryna Saranchova,
- Iryna Saranchova,
- Iryna Saranchova,
- Lonna Munro,
- Lonna Munro,
- Lonna Munro,
- Lonna Munro,
- Cheryl G. Pfeifer,
- Cheryl G. Pfeifer,
- Cheryl G. Pfeifer,
- Cheryl G. Pfeifer,
- Brett A. Eyford,
- Brett A. Eyford,
- Brett A. Eyford,
- Tunc Morova,
- David E. Williams,
- Ping Cheng,
- Nathan A. Lack,
- Nathan A. Lack,
- Raymond J. Andersen,
- Wilfred A. Jefferies,
- Wilfred A. Jefferies,
- Wilfred A. Jefferies,
- Wilfred A. Jefferies,
- Wilfred A. Jefferies,
- Wilfred A. Jefferies
Affiliations
- Samantha L. S. Ellis
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Samantha L. S. Ellis
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Samantha L. S. Ellis
- The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Samantha L. S. Ellis
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada
- Sarah Dada
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Sarah Dada
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Sarah Dada
- The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Sarah Dada
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada
- Sarah Dada
- Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada
- Sarah Dada
- Departments of Medical Genetics, Zoology, and Urologic Sciences, University of British Columbia, Vancouver, BC, Canada
- Lilian L. Nohara
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Lilian L. Nohara
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Lilian L. Nohara
- The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Iryna Saranchova
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Iryna Saranchova
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Iryna Saranchova
- The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Iryna Saranchova
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada
- Iryna Saranchova
- Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada
- Iryna Saranchova
- Departments of Medical Genetics, Zoology, and Urologic Sciences, University of British Columbia, Vancouver, BC, Canada
- Lonna Munro
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Lonna Munro
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Lonna Munro
- The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Lonna Munro
- Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada
- Cheryl G. Pfeifer
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Cheryl G. Pfeifer
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Cheryl G. Pfeifer
- The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Cheryl G. Pfeifer
- Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada
- Brett A. Eyford
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Brett A. Eyford
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Brett A. Eyford
- The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Tunc Morova
- Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada
- David E. Williams
- Departments of Chemistry and Earth Ocean, and Atmospheric Sciences, University of British Columbia, Vancouver, BC, Canada
- Ping Cheng
- Departments of Chemistry and Earth Ocean, and Atmospheric Sciences, University of British Columbia, Vancouver, BC, Canada
- Nathan A. Lack
- Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada
- Nathan A. Lack
- School of Medicine, Koç University, Istanbul, Türkiye
- Raymond J. Andersen
- Departments of Chemistry and Earth Ocean, and Atmospheric Sciences, University of British Columbia, Vancouver, BC, Canada
- Wilfred A. Jefferies
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Wilfred A. Jefferies
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Wilfred A. Jefferies
- The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Wilfred A. Jefferies
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada
- Wilfred A. Jefferies
- Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada
- Wilfred A. Jefferies
- Departments of Medical Genetics, Zoology, and Urologic Sciences, University of British Columbia, Vancouver, BC, Canada
- DOI
- https://doi.org/10.3389/fphar.2023.1119620
- Journal volume & issue
-
Vol. 14
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.
Keywords
- epigenetic modification
- antigen processing machinery
- curcuphenol
- major histocompatibility complex class I
- histone deacetylase activity
- HDAC
