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

Ljungblad, Linda and Bergqvist, Filip and Tummler, Conny and Madawala, Samanthi and Olsen, Thale Kristin and Andonova, Teodora and Jakobsson, Per-Johan and Johnsen, John Inge and Pickova, Jana and Strandvik, Birgitta and Kogner, Per and Gleissman, Helena and Wickstrom, Malin (2022). Omega-3 fatty acids decrease CRYAB, production of oncogenic prostaglandin E-2 and suppress tumor growth in medulloblastoma. Life Sciences. 295 , 120394
[Research article]

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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.

Authors/Creators:Ljungblad, Linda and Bergqvist, Filip and Tummler, Conny and Madawala, Samanthi and Olsen, Thale Kristin and Andonova, Teodora and Jakobsson, Per-Johan and Johnsen, John Inge and Pickova, Jana and Strandvik, Birgitta and Kogner, Per and Gleissman, Helena and Wickstrom, Malin
Title:Omega-3 fatty acids decrease CRYAB, production of oncogenic prostaglandin E-2 and suppress tumor growth in medulloblastoma
Series Name/Journal:Life Sciences
Year of publishing :2022
Volume:295
Article number:120394
Number of Pages:12
Publisher:PERGAMON-ELSEVIER SCIENCE LTD
ISSN:0024-3205
Language:English
Publication Type:Research article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 301 Basic Medicine > Cell and Molecular Biology
Keywords:Docosahexaenoic acid, Eicosapentaenoic acid, Docosapentaenoic acid, Dihomo-gamma-linolenic acid, Prostacyclin, Thromboxane, Pediatric cancer, CRYAB
URN:NBN:urn:nbn:se:slu:epsilon-p-116824
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-116824
Additional ID:
Type of IDID
DOI10.1016/j.lfs.2022.120394
Web of Science (WoS)000777805200001
ID Code:27813
Faculty:NJ - Fakulteten för naturresurser och jordbruksvetenskap
Department:(NL, NJ) > Department of Molecular Sciences
Deposited By: SLUpub Connector
Deposited On:13 May 2022 11:25
Metadata Last Modified:13 May 2022 11:31

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