| Title: |
Omega-3 fatty acids decrease CRYAB, production of oncogenic prostaglandin E-2 and suppress tumor growth in medulloblastoma |
| Authors: |
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 |
| Publication Year: |
2022 |
| Collection: |
Swedish University of Agricultural Sciences / Sveriges Lantbruksuniversitet (SLU): Epsilon Open Archive |
| Subject Terms: |
Cell and Molecular Biology |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://pub.epsilon.slu.se/27813/1/ljungblad-l-et-al-220513.pdf; 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] |
| Availability: |
https://pub.epsilon.slu.se/27813/ |
| Accession Number: |
edsbas.A0E4DFB4 |
| Database: |
BASE |