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Research article - Peer-reviewed, 2022

Omega-3 fatty acids decrease CRYAB, production of oncogenic prostaglandin E-2 and suppress tumor growth in medulloblastoma

Ljungblad, Linda; Bergqvist, Filip; Tummler, Conny; Madawala, Samanthi; Olsen, Thale Kristin; Andonova, Teodora; Jakobsson, Per-Johan; Johnsen, John Inge; Pickova, Jana; Strandvik, Birgitta; Kogner, Per; Gleissman, Helena; Wickstrom, Malin

Abstract

Aims: Medulloblastoma (MB) is one of the most common malignant central nervous system tumors of childhood. Despite intensive treatments that often leads to severe neurological sequelae, the risk for resistant relapses remains significant. In this study we have evaluated the effects of the omega 3-long chain polyunsaturated fatty acids (omega 3-LCPUFA) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on MB cell lines and in a MB xenograft model.Main methods: Effects of omega 3-LCPUFA treatment of MB cells were assessed using the following: WST-1 assay, cell death probes, clonogenic assay, ELISA and western blot. MB cells were implanted into nude mice and the mice were randomized to DHA, or a combination of DHA and EPA treatment, or to control group. Treatment effects in tumor tissues were evaluated with: LC-MS/MS, RNA-sequencing and immunohistochemistry, and tumors, erythrocytes and brain tissues were analyzed with gas chromatography.Key findings: omega 3-LCPUFA decreased prostaglandin E2 (PGE(2)) secretion from MB cells, and impaired MB cell viability and colony forming ability and increased apoptosis in a dose-dependent manner. DHA reduced tumor growth in vivo, and both PGE(2) and prostacyclin were significantly decreased in tumor tissue from treated mice compared to control animals. All omega 3-LCPUFA and dihomo-gamma-linolenic acid increased in tumors from treated mice. RNA-sequencing revealed 10 downregulated genes in common among omega 3-LCPUFA treated tumors. CRYAB was the most significantly altered gene and the downregulation was confirmed by immunohistochemistry.Significance: Our findings suggest that addition of DHA and EPA to the standard MB treatment regimen might be a novel approach to target inflammation in the tumor microenvironment.

Keywords

Docosahexaenoic acid; Eicosapentaenoic acid; Docosapentaenoic acid; Dihomo-gamma-linolenic acid; Prostacyclin; Thromboxane; Pediatric cancer; CRYAB

Published in

Life Sciences
2022, volume: 295, article number: 120394
Publisher: PERGAMON-ELSEVIER SCIENCE LTD

Authors' information

Ljungblad, Linda
Karolinska Institutet
Bergqvist, Filip
Karolinska Institutet
Tummler, Conny
Karolinska Institutet
Madawala, Samanthi
Swedish University of Agricultural Sciences, Department of Molecular Sciences
Olsen, Thale Kristin
Karolinska Institutet
Andonova, Teodora
Karolinska Institutet
Jakobsson, Per-Johan
Karolinska Institutet
Johnsen, John Inge
Karolinska Institutet
Swedish University of Agricultural Sciences, Department of Molecular Sciences
Strandvik, Birgitta
Karolinska Institutet
Kogner, Per
Karolinska Institutet
Gleissman, Helena
Karolinska Institutet
Wickstrom, Malin
Karolinska Institutet

UKÄ Subject classification

Cell and Molecular Biology

Publication Identifiers

DOI: https://doi.org/10.1016/j.lfs.2022.120394

URI (permanent link to this page)

https://res.slu.se/id/publ/116824