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A glioma is a type of tumor that acts on the Central Nervous System (CNS) in a highly aggressive manner. Gliomas can occasionally be inaccurately diagnosed and treatments have low efficacy, meaning that patients exhibit a survival of less than one year after diagnosis. Due to factors such as intratumoral cell variability, inefficient chemotherapy drugs, adaptive resistance development to drugs and tumor recurrence after resection, the search continues for new drugs that can inhibit glioma cell growth. As such, analogues of endocannabinoids, such as fatty acid amides (FAAs), represent interesting alternatives for inhibiting tumor growth, since FAAs can modulate several metabolic pathways linked to cancer and, thus, may hold potential for managing glioblastoma. The aim of this study was to investigate the in vitro effects of two fatty ethanolamides (FAA1 and FAA2), synthetized via direct amidation from andiroba oil (Carapa guianensis Aublet), on C6 glioma cells. FAA1 and FAA2 reduced C6 cell viability, proliferation and migratory potential in a dose-dependent manner and were not toxic to normal retina glial cells. Both FAAs caused apoptotic cell death through the loss of mitochondrial integrity (ΔΨm), probably by activating cannabinoid receptors, and inhibiting the PI3K/Akt pathway. In conclusion, FAAs derived from natural products may have the potential to treat glioma-type brain cancer. [ABSTRACT FROM AUTHOR]

The production of polyunsaturated fatty acids from fish oil, which is related to various health benefits including effects against cardiovascular diseases, antihypertensive, anticancer, antioxidant, antidepression, anti-aging, and anti-arthritis effects, among others, can be advantageously performed through the application of lipase. However, the high cost associated with enzyme production can make the process unfeasible and thus alternative substrates should be investigated to solve these problems. This research aimed to produce lipase by Yarrowia lipolytica IMUFRJ50682 in solid-state fermentation using by-products of the food processing industry (andiroba oil cake and soybean meal) and verify the potential application in the initial hydrolysis of fish oil to further produce polyunsaturated fatty acids in a suitable process. A screening was carried out for the analysis of andiroba oil cake and soybean meal combinations in different proportions (0:100 to 100:0, respectively) at 48 h of the fermentation process. Afterward, the solid matrix composed by soybean meal and andiroba oil cake was supplemented with soy oil and Tween 80 to improve the lipase activity. The enzymatic extract was characterized in relation to the protein profile by electrophoresis. Finally, the enzymatic extract and the solid biocatalyst produced were applied to evaluate the potential hydrolysis of the fish oil in an initial study. Maximum lipolytic activity (63.7 U·g−1) was achieved using andiroba oil cake and soybean meal (50:50) after 24 h of fermentation. Soybean oil 1.5% and Tween 80 (0.001%) in an emulsion provided an increase of 1.5-fold (82.52 U·g−1) in the enzyme activity. The electrophoretic analysis demonstrated a band between 37 and 40 kDa that may be related to lipase and a band of 75 kDa referring to the α subunit of the β-conglycinin present in soybean meal. After 48 h, the solid biocatalyst showed a higher degree of hydrolysis (DH) (71.0%) than the enzymatic extract (61.5%). The solid biocatalyst was stable during storage at room temperature for 7 months. The production of lipases using Amazon fruit by-product and soybean meal in solid-state fermentation is viable as well as the application of the extract and solid biocatalyst in the initial application for the hydrolysis of fish oil to further produce polyunsaturated fatty acids in an industrially suited process. [ABSTRACT FROM AUTHOR]