Astaxanthin Increases Tumor Suppressor Gene Expression and Affects Cellular Biological Behavior in Oral Dysplastic

Peiyan Wang1,2, Xiaofei Yu1,2, Pei Sun1,2

  • 1Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao, China.

Abstract

Insights

Astaxanthin reduces tumor suppressor gene promoter methylation in oral dysplasia, inhibiting cell viability and migration. This study clarifies astaxanthin

Area of Science:

  • Oral oncology
  • Epigenetics
  • Nutritional biochemistry

Background:

  • Abnormal DNA methylation inactivates tumor suppressor genes (TSGs) in oral potential malignant diseases (OPMDs).
  • Carotenoids, such as astaxanthin, show therapeutic potential in OPMDs and oral squamous cell carcinoma (OSCC) by regulating DNA methylation.

Purpose of the Study:

  • To investigate the relationship between astaxanthin's anti-cancer effects and its DNA methylation regulatory capacity in OPMDs.
  • To elucidate the molecular mechanisms underlying astaxanthin's action on oral dysplastic keratinocytes (DOK) cells.

Main Methods:

  • Whole-genome bisulfite sequencing (WGBS) for comprehensive DNA methylation analysis.
  • Methylation-specific PCR, qRT-PCR, and Western blot to assess gene and protein expression.
  • Cell viability (CCK8), migration (scratch assay), cell cycle, and apoptosis assays to evaluate cellular responses to astaxanthin.

Main Results:

  • WGBS identified significant promoter CpG methylation differences in TSGs HOXA3 and SOX1 in DOK cells.
  • Astaxanthin treatment (8 μM) reduced promoter CpG methylation of these TSGs, leading to increased gene expression.
  • Astaxanthin inhibited DOK cell viability, reduced migration, induced G0/G1 cell cycle arrest, and promoted apoptosis.

Conclusions:

  • Significant variations in DNA methylation patterns exist between normal, dysplastic, and cancerous oral cells.
  • Astaxanthin downregulates DNA methyltransferase 1 (DNMT1) protein expression, reducing TSG promoter CpG methylation.
  • Astaxanthin modulates the biological behavior of DOK cells by upregulating TSG expression, offering therapeutic potential for OPMDs.

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