Abstract
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.
Highlights
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor
We found that complete depletion of lipid droplets (LDs) reduced the cell survival rate of glioma cells treated with oleic acid (OA) or eicosapentaenoic acid (EPA), but rescued palmitic acid (PA)-treated cells to some extent
We observed that glioma cells produced more LDs upon free fatty acids (FAs) treatment
Summary
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor. The effectiveness of traditional therapies for GBM is limited and new therapies are highly desired. Previous studies show that lipid metabolism reprogramming may be a potential therapeutic target in GBM. 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. 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. Glioma cells exhibit altered lipid metabolic activities, including elevated uptake of free FAs or de novo lipogenesis. It is known that the process of adipogenesis converts cytotoxic free FAs into non-toxic neutral lipids, which provides a protective mechanism for cells to Scientific Reports | (2021) 11:7422
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