Omega-3 fatty acids decrease CRYAB, production of oncogenic prostaglandin E2 and suppress tumor growth in

Linda Ljungblad1, Filip Bergqvist2, Conny Tümmler1

  • 1Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.

Life Sciences
|February 14, 2022
PubMed
Abstract

Insights

Omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), reduced medulloblastoma (MB) cell growth and tumor progression. These ω3-long chain polyunsaturated fatty acids (ω3-LCPUFA) show potential for targeting MB inflammation.

Area of Science:

  • Neuro-oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Medulloblastoma (MB) is a common pediatric central nervous system malignancy.
  • Current treatments for MB carry risks of severe neurological side effects and significant relapse rates.
  • Targeting tumor microenvironment inflammation is a potential therapeutic strategy.

Purpose of the Study:

  • To evaluate the effects of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), which are ω3-long chain polyunsaturated fatty acids (ω3-LCPUFA), on medulloblastoma (MB) cell lines.
  • To assess the efficacy of DHA and EPA in a medulloblastoma xenograft model.

Main Methods:

  • In vitro: WST-1 assay, cell death probes, clonogenic assay, ELISA, and western blot were used to assess MB cell responses to ω3-LCPUFA.
  • In vivo: MB xenograft model in nude mice treated with DHA, DHA+EPA, or control. Tumor tissues, erythrocytes, and brain tissues were analyzed using LC-MS/MS, RNA-sequencing, immunohistochemistry, and gas chromatography.

Main Results:

  • ω3-LCPUFA dose-dependently reduced MB cell viability, colony formation, and increased apoptosis, while decreasing prostaglandin E2 (PGE2) secretion.
  • DHA treatment significantly inhibited tumor growth in vivo, with decreased PGE2 and prostacyclin in tumor tissues.
  • RNA-sequencing identified common downregulated genes in treated tumors, notably CRYAB, confirmed by immunohistochemistry.

Conclusions:

  • DHA and EPA demonstrate anti-tumor effects in medulloblastoma models.
  • Supplementation with DHA and EPA may offer a novel approach to manage MB by targeting tumor microenvironment inflammation.

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