蜜蜂幼虫早期发育过程中蜂王浆 (RJ) 的差异饮食塑造了表型，这可能是由基因表达的表观遗传调控介导的。有证据表明，RJ 中的小分子可以调节哺乳动物细胞中的基因表达，例如脂肪酸 10-羟基-2-癸烯酸 (10-HDA)，以前与组蛋白脱乙酰酶 (HDAC) 的抑制有关。因此，我们结合计算（分子对接模拟）和实验方法在 32 种 RJ 衍生脂肪酸中筛选潜在的 HDAC 抑制剂 (HDACi)。进行生化测定和基因表达分析（逆转录酶 - 定量聚合酶链反应）以评估主要 RJ 脂肪酸 10-HDA 和 10-HDAA（10-羟基癸酸）在两种人类癌细胞中的功能作用线（HCT116 和 MDA-MB-231）。分子对接模拟表明，这些脂肪酸可能与 I 类 HDAC 相互作用，特别是与人 HDAC2 的催化结构域相互作用，同样与众所周知的 HDAC 抑制剂 (HDACi) 如 SAHA（辛二酰苯胺异羟肟酸）和 TSA（曲古抑菌素 A）相互作用。此外，10-HDA和10-HDAA联合治疗可抑制人核HDAC的活性，导致癌细胞中HDAC编码基因的表达略有增加。我们的研究结果表明，蜂王浆脂肪酸共同有助于抑制 HDAC，而 10-HDA 和 10-HDAA 是弱 HDACi，可促进染色质赖氨酸残基的乙酰化，从而引发癌细胞基因表达水平的增加。

A differential diet with royal jelly (RJ) during early larval development in honeybees shapes the phenotype, which is probably mediated by epigenetic regulation of gene expression. Evidence indicates that small molecules in RJ can modulate gene expression in mammalian cells, such as the fatty acid 10-hydroxy-2-decenoic acid (10-HDA), previously associated with the inhibition of histone deacetylase enzymes (HDACs). Therefore, we combined computational (molecular docking simulations) and experimental approaches for the screening of potential HDAC inhibitors (HDACi) among 32 RJ-derived fatty acids. Biochemical assays and gene expression analyses (Reverse Transcriptase - quantitative Polymerase Chain Reaction) were performed to evaluate the functional effects of the major RJ fatty acids, 10-HDA and 10-HDAA (10-hydroxy-decanoic acid), in two human cancer cell lines (HCT116 and MDA-MB-231). The molecular docking simulations indicate that these fatty acids might interact with class I HDACs, specifically with the catalytic domain of human HDAC2, likewise well-known HDAC inhibitors (HDACi) such as SAHA (suberoylanilide hydroxamic acid) and TSA (Trichostatin A). In addition, the combined treatment with 10-HDA and 10-HDAA inhibits the activity of human nuclear HDACs and leads to a slight increase in the expression of HDAC-coding genes in cancer cells. Our findings indicate that royal jelly fatty acids collectively contribute to HDAC inhibition and that 10-HDA and 10-HDAA are weak HDACi that facilitate the acetylation of lysine residues of chromatin, triggering an increase in gene expression levels in cancer cells.