Glioma cells survival depends both on fatty acid oxidation and on functional carnitine transport by SLC22A5

Gliomas are the most common primary malignant brain tumor in adults, but current treatment for glioblastoma multiforme (GBM) is insufficient. Even though glucose is the primary energetic substrate of glioma cells, they are capable of using fatty acids to generate energy. Fatty acid oxidation (FAO) in mitochondria requires L‐carnitine for the formation of acylcarnitines by carnitine palmitoylotransferase 1 (CPT1) and further transport of acyl carnitine esters to mitochondrial matrix. Carnitine can be delivered to the cell by an organic cation/carnitine transporter—SLC22A5/OCTN2. In this study, we show that SLC22A5 is up‐regulated in glioma cells and that they vary in the amount of SLC22A5 in the plasma membrane. Research on glioma cells (lines U87MG, LN229, T98G) with various expression levels of SLC22A5 demonstrated a correlation between the FAO rate, the level of the transporter, and the carnitine transport. Inhibition of carnitine transport by chemotherapeutics, such as vinorelbine and vincristine, led to inhibition of FAO, which was further intensified by etomoxir—a CPT1 inhibitor. This led to reduced viability and increased apoptosis in glioma cells. Modulation of SLC22A5 level by either silencing or up‐regulation of SLC22A5 also affected glioma cell survival in a FAO‐dependent way. These observations suggest that the survival of glioma cells is heavily reliant on both FAO and SLC22A5 activity, as well as that CPT1 and SLC22A5 might be possible drug targets. Glioma cells are capable of using fatty acids to generate energy. Inhibition of SLC22A5‐dependent carnitine transport by chemotherapeutics, such as vinorelbine and vincristine, led to inhibition of fatty acid oxidation (FAO), which was further intensified by etomoxir, a CPT1 inhibitor. This led to reduced viability and increased apoptosis in glioma cells. The survival of glioma cells is heavily reliant on both FAO and SLC22A5 activity, as well as that CPT1 and SLC22A5 might be possible drug targets and thus an important step towards treatment of the most common primary malignant brain tumor in adults.