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
Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada.
Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada.
Front Pharmacol. 2023 Aug 10;14:1119620. doi: 10.3389/fphar.2023.1119620. eCollection 2023.
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.
姜黄酚是烹饪香料中的常见成分，天然存在于海洋无脊椎动物和植物中，已被确定为一种新型候选物质，可通过恢复侵袭性癌症中抗原呈递机制（APM）的表达来逆转免疫逃逸，从而恢复对转移性肿瘤的免疫识别。通过合理设计制备了两种合成姜黄酚类似物，它们在转移性前列腺癌和肺癌细胞中均能持续诱导APM表达。随后发现这两种类似物均具有一种先前未描述的增强组蛋白脱乙酰基酶（HDAC）的活性。值得注意的是，对姜黄酚处理的细胞进行的H3K27ac ChIPseq分析表明，诱导的表观基因组标记与用γ-干扰素观察到的全基因组模式变化非常相似，γ-干扰素是一种在协调先天免疫和适应性免疫中起重要作用的细胞因子。这些观察结果将饮食成分与修饰表观遗传程序联系起来，这些表观遗传程序可调节指导平衡免疫的基因表达。
