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

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 ω3-long chain polyunsaturated fatty acids (ω3-LCPUFA) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on MB cell lines and in a MB xenograft model. MAIN METHODS: Effects of ω3-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: ω3-LCPUFA decreased prostaglandin E2 (PGE2) 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 PGE2 and prostacyclin were significantly decreased in tumor tissue from treated mice compared to control animals. All ω3-LCPUFA and dihomo-γ-linolenic acid increased in tumors from treated mice. RNA-sequencing revealed 10 downregulated genes in common among ω3-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.

In vitro biodegradation of cyanotoxins in the rumen fluid of cattle.

BACKGROUND: In countries around the Baltic Sea grazing ruminants have access to and drink, surface water from lakes, rivers and in several coastal regions. The water quality of these naturally occurring reservoirs affects performance and health of livestock. In the Baltic Sea both microcystin (MC) and nodularin (NOD) occurs as cyclic peptides and have hepatotoxic effects. Although cattle obviously have died after consuming contaminated water very little information is available as to how susceptible ruminants are to the toxins produced by cyanobacteria. The critical question as to whether the rumen microflora might constitute a protective shield is unresolved. For this reason our aim is to investigate a possible degradation rate of these toxins in rumen. RESULTS: The ability of rumen microorganisms to degrade certain important cyanotoxins (MC-LR, YR, RR and NOD) was studied in vitro by incubating with rumen fluid at three different concentrations (0.05, 0.5 and 5 µg/mL) for 3 h. The degradation efficiencies were determined by LC-MS (ESI) positive mode. Degradation was observed in the following order MC-RR 36%, NOD 35%, MC-RR 25% and MC-LR 8.9% at lower concentrations within 3 h. However, average degradation was observed at concentration of 0.5 µg/mL. No degradation was observed in higher concentrations for entire 3 h. The present results reveal that the degradation was both dose and time dependent. CONCLUSIONS: In conclusion the present results suggest that the rumen microbial flora may protect ruminants from being intoxicated by Cyanotoxins.

Novel Conjugates of 1,3-Diacylglycerol and Lipoic Acid: Synthesis, DPPH Assay, and RP-LC-MS-APCI Analysis.

1,3-Diacylglycerol is known to reduce body weight and fat deposits in humans. α-Lipoic acid is a potent antioxidant and effective against many pathological conditions, including obesity and related metabolic syndromes. The present work is based on the hypothesis that the hybrid molecules of 1,3-diacylglycerol and lipoic acid possess synergistic and/or additive effects compared with the parent compounds against obesity, overweight, and related metabolic syndromes. Laboratory scale synthesis of 1,3-dioleoyl-2-lipoyl-sn-glycerol (yield 80%) and 1,3-dioleoyl-2-dihydrolipoyl-sn-glycerol (yield 70%) was performed for the first time and supported by NMR and MS data. Free radical scavenging capacity of the conjugates was assayed using DPPH test. A remarkably high in vitro free radical scavenging capacity was demonstrated for the 1,3-dioleoyl-2-dihydrolipoyl-sn-glycerol (EC(50) value 0.21). RP-HPLC-MS-APCI analysis showed satisfactory separation between the conjugates (R~1). Protonated molecular ion of the conjugates at m/z 809 and m/z at 811, respectively, and their characteristic fragment ions were abundant.