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

Autor: Samantha L. S. Ellis, Sarah Dada, Lilian L. Nohara, Iryna Saranchova, Lonna Munro, Cheryl G. Pfeifer, Brett A. Eyford, Tunc Morova, David E. Williams, Ping Cheng, Nathan A. Lack, Raymond J. Andersen, Wilfred A. Jefferies
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Frontiers in Pharmacology, Vol 14 (2023)
Druh dokumentu: article
ISSN: 1663-9812
DOI: 10.3389/fphar.2023.1119620
Popis: 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.
Databáze: Directory of Open Access Journals