Influence of Lipoxygenase Inhibition on Glioblastoma Cell Biology

• Published in: International journal of molecular sciences 2020-11, Vol.21 (21), p.8395
• Main Authors: Souza, Felipe da Costa, Ferreira, Matthew Thomas, Colquhoun, Alison
• Format: Article
• Language: English
• Subjects: Arachidonate 15-Lipoxygenase - metabolism; Cell Cycle Checkpoints - drug effects; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; G2 Phase Cell Cycle Checkpoints - drug effects; Glioblastoma - drug therapy; Glioblastoma - metabolism; Glioma - drug therapy; Glioma - metabolism; Humans; Linoleic Acid - metabolism; Linoleic Acids - metabolism; Linoleic Acids, Conjugated - metabolism; Lipoxygenase Inhibitors - pharmacology
• ISSN: 1422-0067; 1422-0067
• DOI: 10.3390/ijms21218395

The relationship between glioblastoma (GBM) and fatty acid metabolism could be the key to elucidate more effective therapeutic targets. 15-lipoxygenase-1 (15-LOX), a linolenic acid and arachidonic acid metabolizing enzyme, induces both pro- and antitumorigenic effects in different cancer types. Its role in glioma activity has not yet been clearly described. The objective of this study was to identify the influence of 15-LOX and its metabolites on glioblastoma cell activity. GBM cell lines were examined using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to identify 15-LOX metabolites. GBM cells treated with 15-LOX metabolites, 13-hydroxyoctadecadeinoic acid (HODE) and 9-HODE, and two 15-LOX inhibitors (luteolin and nordihydroguaiaretic acid) were also examined. Dose response/viability curves, RT-PCRs, flow cytometry, migration assays, and zymograms were performed to analyze GBM growth, migration, and invasion. Higher quantities of 13-HODE were observed in five GBM cell lines compared to other lipids analyzed. Both 13-HODE and 9-HODE increased cell count in U87MG. 15-LOX inhibition decreased migration and increased cell cycle arrest in the G2/M phase. 15-LOX and its linoleic acid (LA)-derived metabolites exercise a protumorigenic influence on GBM cells in vitro. Elevated endogenous levels of 13-HODE called attention to the relationship between linoleic acid metabolism and GBM cell activity.