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β-hydroxybutyrate impairs nasopharyngeal carcinoma cell aggressiveness via histone deacetylase 4 inhibition

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Abstract

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.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Otolaryngology, The Affiliated Hospital of Putian University, No. 999 Dongzhen East Road, Licheng District, Putian City, 351100, Fujian Province, China

    Jinqiao Huang, Xian Chen, Hong Lin & Xiufen Chen

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  1. Jinqiao Huang
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  2. Xian Chen
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  3. Hong Lin
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  4. Xiufen Chen
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Contributions

JH designed the research plan. JH, XC, HL, and XC performed the experiments and analyzed the data. JH and XC wrote the manuscript.

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Correspondence to Jinqiao Huang.

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Huang, J., Chen, X., Lin, H. et al. β-hydroxybutyrate impairs nasopharyngeal carcinoma cell aggressiveness via histone deacetylase 4 inhibition. Mol. Cell. Toxicol. (2023). https://doi.org/10.1007/s13273-023-00378-7

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