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Sci Rep ; 11(1): 7422, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33795756

RESUMO

Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor. The effectiveness of traditional therapies for GBM is limited and therefore new therapies are highly desired. Previous studies show that lipid metabolism reprogramming may be a potential therapeutic target in GBM. This study aims to evaluate the therapeutic potential of free fatty acid-induced lipotoxicity for the suppression of glioma growth. U87 glioma cells are treated with three fatty acids (FAs): palmitic acid (PA), oleic acid (OA), and eicosapentaenoic acid (EPA). Uptake of the FAs and formation of lipid droplets (LDs) are imaged and quantified using a lab-built stimulated Raman scattering (SRS) microscope. Our results show that a supply of 200 µM PA, OA, and EPA leads to efficient LDs accumulation in glioma cells. We find that inhibition of triglycerides (TAGs) synthesis depletes LDs and enhances lipotoxicity, which is evidenced by the reduced cell proliferation rates. In particular, our results suggest that EPA treatment combined with depletion of LDs significantly reduces the survival rate of glioma cells by more than 50%, indicating the therapeutic potential of this approach. Future work will focus on understanding the metabolic mechanism of EPA-induced lipotoxicity to further enhance its anticancer effects.


Assuntos
Ácidos Graxos/química , Ácidos Graxos/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Microscopia Óptica não Linear , Biomarcadores , Neoplasias Encefálicas , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Diacilglicerol O-Aciltransferase/metabolismo , Ácidos Graxos/efeitos adversos , Glioblastoma , Humanos , Processamento de Imagem Assistida por Computador , Lipogênese/efeitos dos fármacos , Redes e Vias Metabólicas/efeitos dos fármacos , Microscopia de Fluorescência/métodos , Microscopia Óptica não Linear/métodos , Imagem Óptica/métodos
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