Influence of Serum and Hypoxia on Incorporation of [¹⁴C]‐d‐Glucose or [¹⁴C]‐l‐Glutamine into Lipids and Lactate in Murine Glioblastoma Cells

Abstract

Glucose and glutamine are essential energy metabolites for brain tumor growth and survival under both normoxic and hypoxic conditions. Both metabolites can contribute their carbons to lipid biosynthesis. We used uniformly labeled [(14)C]-U-D-glucose and [(14)C]-U-L-glutamine to examine the profile of de novo lipid biosynthesis in the VM-M3 murine glioblastoma cells. The major lipids synthesized included phosphatidylcholine (PtdCho), phosphatidylethanolamine (EtnGpl), phosphatidylinositol (PtdIns), phosphatidylserine (PtdSer), sphingomyelin (CerPCho), bis(monoacylglycero)phosphate (BMP)/phosphatidic acid (PtdOH), cholesterol (C), cardiolipin (Ptd2Gro), and gangliosides. Endogenous lipid synthesis, using either glucose or glutamine, was greater in media without fetal bovine serum (FBS) than in media containing 10 % FBS under normoxia. De novo lipid synthesis was greater using glucose carbons than glutamine carbons under normoxia. The reverse was observed for most lipids under hypoxia suggesting an attenuation of glucose entering the TCA cycle. Lactate was produced largely from glucose carbons with minimal lactate derived from glutamine under either normoxia or hypoxia. Accumulation of triacylglycerols (TAG), containing mostly saturated and mono-unsaturated fatty acids, was observed under hypoxia using carbons from either glucose or glutamine. The data show that the incorporation of labeled glucose and glutamine into most synthesized lipids was dependent on the type of growth environment, and that the VM-M3 glioblastoma cells could acquire lipids, especially cholesterol, from the external environment for growth and proliferation.

Complex I inhibition augments dichloroacetate cytotoxicity through enhancing oxidative stress in VM-M3 glioblastoma cells

“…VM-M3 cells are derived from an extremely aggressive spontaneous mouse brain tumor and exhibit a dependency on glycolytic metabolism [41, 42]. We have previously established that this tumor is susceptible to therapeutic metabolic modulation [43–45].…”

Press-pulse: a novel therapeutic strategy for the metabolic management of cancer

“…Glutamine metabolism can produce ATP from the TCA cycle under aerobic conditions. Glutamine is also a nitrogen donor for nucleotide biosynthesis and can serve as precursor for lipid synthesis under hypoxic conditions [ 104 , 105 ]. We also found that only minor amounts of glutamine are metabolized to lactic acid under either normoxia or hypoxia in the VM-M3 invasive glioblastoma cells consistent with findings in other tumor cells [ 105 – 107 ].…”

Consideration of Ketogenic Metabolic Therapy as a Complementary or Alternative Approach for Managing Breast Cancer

“…Many tumor cells including breast cancer cells will store fatty acids as lipid droplets (166,171,172). Lipid droplet storage is considered a protection mechanism from the lethal effects of saturated fatty acids in cells that cannot metabolize fats for energy (171)(172)(173)(174). If tumor cells could use fatty acids for growth, then water-only fasting and calorie restricted ketogenic diets should accelerate tumor growth, as these dietary changes elevate free fatty acids in the blood (175,176).…”