Frontiers in Pharmacology (May 2023)
A novel cell-based screen identifies chemical entities that reverse the immune-escape phenotype of metastatic tumours
- Lilian L. Nohara,
- Lilian L. Nohara,
- Lilian L. Nohara,
- Samantha L. S. Ellis,
- Samantha L. S. Ellis,
- Samantha L. S. Ellis,
- Samantha L. S. Ellis,
- Carola Dreier,
- Carola Dreier,
- Carola Dreier,
- Sarah Dada,
- Sarah Dada,
- Sarah Dada,
- Sarah Dada,
- Sarah Dada,
- Sarah Dada,
- Iryna Saranchova,
- Iryna Saranchova,
- Iryna Saranchova,
- Iryna Saranchova,
- Iryna Saranchova,
- Iryna Saranchova,
- Kyong Bok Choi,
- Lonna Munro,
- Lonna Munro,
- Lonna Munro,
- Lonna Munro,
- Cheryl G. Pfeifer,
- Cheryl G. Pfeifer,
- Cheryl G. Pfeifer,
- Cheryl G. Pfeifer,
- Eliana Al Haddad,
- Krysta M. Coyle,
- Krysta M. Coyle,
- Krysta M. Coyle,
- Krysta M. Coyle,
- Krysta M. Coyle,
- Jessica R. Morrice,
- Jessica R. Morrice,
- Jessica R. Morrice,
- Jessica R. Morrice,
- Jessica R. Morrice,
- Daniel Joo Sung Shim,
- Daniel Joo Sung Shim,
- Daniel Joo Sung Shim,
- Daniel Joo Sung Shim,
- Paul Ahn,
- Paul Ahn,
- Paul Ahn,
- Paul Ahn,
- Paul Ahn,
- Nicole De Voogd,
- David E. Williams,
- Ping Cheng,
- Emmanuel Garrovillas,
- Emmanuel Garrovillas,
- Raymond J. Andersen,
- Wilfred A. Jefferies,
- Wilfred A. Jefferies,
- Wilfred A. Jefferies,
- Wilfred A. Jefferies,
- Wilfred A. Jefferies,
- Wilfred A. Jefferies
Affiliations
- 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
- 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
- Carola Dreier
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Carola Dreier
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Carola Dreier
- The Djavad Mowafaghian Centre for Brain Health, 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
- 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
- Kyong Bok Choi
- Michael Smith Laboratories, 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
- Eliana Al Haddad
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Krysta M. Coyle
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Krysta M. Coyle
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Krysta M. Coyle
- The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Krysta M. Coyle
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada
- Krysta M. Coyle
- Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada
- Jessica R. Morrice
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Jessica R. Morrice
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Jessica R. Morrice
- The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Jessica R. Morrice
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada
- Jessica R. Morrice
- Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC, Canada
- Daniel Joo Sung Shim
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Daniel Joo Sung Shim
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Daniel Joo Sung Shim
- The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Daniel Joo Sung Shim
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada
- Paul Ahn
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Paul Ahn
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Paul Ahn
- The Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada
- Paul Ahn
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada
- Paul Ahn
- Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada
- Nicole De Voogd
- Netherlands Centre for Biodiversity Naturalis, Leiden, Netherlands
- David E. Williams
- 0Departments of Chemistry and Earth Ocean and Atmospheric Sciences, University of British Columbia, Vancouver, BC, Canada
- Ping Cheng
- 0Departments of Chemistry and Earth Ocean and Atmospheric Sciences, University of British Columbia, Vancouver, BC, Canada
- Emmanuel Garrovillas
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
- Emmanuel Garrovillas
- Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada
- Raymond J. Andersen
- 0Departments 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.2023.1119607
- Journal volume & issue
-
Vol. 14
Abstract
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.
Keywords
- antigen processing machinery
- curcuphenol
- major histocompatibility complex class I
- metastatic tumours
- natural products
- high throughput cell-based assay
