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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Influence of Lipoxygenase Inhibition on Glioblastoma Cell Biology

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Author(s):
Souza, Felipe da Costa [1] ; Ferreira, Matthew Thomas [1] ; Colquhoun, Alison [1]
Total Authors: 3
Affiliation:
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, BR-03001000 Sao Paulo - Brazil
Total Affiliations: 1
Document type: Journal article
Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 21, n. 21 NOV 2020.
Web of Science Citations: 0
Abstract

Background: 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. Methods: 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. Results: 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. Conclusion: 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. (AU)

FAPESP's process: 15/08777-0 - Eicosanoids and the biology of gliomas: influence upon cell proliferation and migration and the response to chemotherapeutic drugs
Grantee:Alison Colquhoun
Support Opportunities: Regular Research Grants