Background

Cancer stem cell phenotype confers tumor aggressiveness in multiple malignancies, including nasopharyngeal carcinoma (NPC). Many studies supported that β-hydroxybutyrate (BHB), a ketone body, acts as an epigenetic factor with an anticancer effect. Nevertheless, the effects of BHB on NPC remain elusive.

Objective

This study explored whether BHB suppressed the aggressive phenotype of NPC cells by suppressing their stemness-like characteristics and exerting an anti-NPC effect.

Results

The proliferation, migration, and invasion abilities of NPC cells after BHB intervention were attenuated, the protein levels of E-cadherin were downregulated, that of N-cadherin and vimentin were upregulated, the volume and number of cell spheres were reduced, and the number of CD44 + cells (cell surface stem cell marker) was reduced. Knockdown of HDAC4 abrogated the effects of BHB on cell proliferation, invasive phenotype, and stemness. The molecular docking map of BHB-HDAC4 displayed that BHB binds the catalytic domain in HDAC4, speculating that BHB functions as an HDAC4-specific inhibitor, preventing the catalytic function of HDAC4 protein rather than inhibiting the translational synthesis of HDAC4 protein.

Conclusions

BHB inhibited NPC cells’ proliferation, stemness characteristics, and invasive phenotypes by specifically restraining HDAC4 expression.

中文翻译：

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β-羟基丁酸通过抑制组蛋白脱乙酰酶 4 损害鼻咽癌细胞的侵袭性

背景

癌症干细胞表型赋予多种恶性肿瘤肿瘤侵袭性，包括鼻咽癌（NPC）。许多研究支持酮体β-羟基丁酸（BHB）作为表观遗传因子具有抗癌作用。然而，BHB 对 NPC 的影响仍然难以捉摸。

客观的

本研究探讨了 BHB 是否通过抑制 NPC 细胞的干性特征并发挥抗 NPC 作用来抑制其侵袭性表型。

结果

BHB干预后鼻咽癌细胞增殖、迁移、侵袭能力减弱，E-cadherin蛋白水平下调，N-cadherin、vimentin蛋白水平上调，细胞球体积和数量减少，细胞数量减少。 CD44 + 细胞（细胞表面干细胞标记）减少。HDAC4 的敲低消除了 BHB 对细胞增殖、侵袭表型和干性的影响。BHB-HDAC4的分子对接图显示BHB与HDAC4中的催化结构域结合，推测BHB作为HDAC4特异性抑制剂，阻止HDAC4蛋白的催化功能而不是抑制HDAC4蛋白的翻译合成。

结论

BHB 通过特异性抑制 HDAC4 表达来抑制 NPC 细胞的增殖、干性特征和侵袭表型。