Synthesis and Significance of Arachidonic Acid, a Substrate for Cyclooxygenases, Lipoxygenases, and Cytochrome P450 Pathways in the Tumorigenesis of Glioblastoma Multiforme, Including a Pan-Cancer Comparative Analysis

Jan Korbecki; Ewa Rębacz-Maron; Patrycja Kupnicka; Dariusz Chlubek; Irena Baranowska-Bosiacka

doi:10.3390/cancers15030946

Synthesis and Significance of Arachidonic Acid, a Substrate for Cyclooxygenases, Lipoxygenases, and Cytochrome P450 Pathways in the Tumorigenesis of Glioblastoma Multiforme, Including a Pan-Cancer Comparative Analysis

Cancers (Basel). 2023 Feb 2;15(3):946. doi: 10.3390/cancers15030946.

Authors

Jan Korbecki¹, Ewa Rębacz-Maron², Patrycja Kupnicka¹, Dariusz Chlubek¹, Irena Baranowska-Bosiacka¹

Affiliations

¹ Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powstańców Wlkp. 72, 70-111 Szczecin, Poland.
² Department of Ecology and Anthropology, Institute of Biology, University of Szczecin, Wąska 13, 71-415 Szczecin, Poland.

Abstract

Glioblastoma multiforme (GBM) is one of the most aggressive gliomas. New and more effective therapeutic approaches are being sought based on studies of the various mechanisms of GBM tumorigenesis, including the synthesis and metabolism of arachidonic acid (ARA), an omega-6 polyunsaturated fatty acid (PUFA). PubMed, GEPIA, and the transcriptomics analysis carried out by Seifert et al. were used in writing this paper. In this paper, we discuss in detail the biosynthesis of this acid in GBM tumors, with a special focus on certain enzymes: fatty acid desaturase (FADS)1, FADS2, and elongation of long-chain fatty acids family member 5 (ELOVL5). We also discuss ARA metabolism, particularly its release from cell membrane phospholipids by phospholipase A₂ (cPLA₂, iPLA₂, and sPLA₂) and its processing by cyclooxygenases (COX-1 and COX-2), lipoxygenases (5-LOX, 12-LOX, 15-LOX-1, and 15-LOX-2), and cytochrome P450. Next, we discuss the significance of lipid mediators synthesized from ARA in GBM cancer processes, including prostaglandins (PGE₂, PGD₂, and 15-deoxy-Δ^12,14-PGJ₂ (15d-PGJ₂)), thromboxane A₂ (TxA₂), oxo-eicosatetraenoic acids, leukotrienes (LTB₄, LTC₄, LTD₄, and LTE₄), lipoxins, and many others. These lipid mediators can increase the proliferation of GBM cancer cells, cause angiogenesis, inhibit the anti-tumor response of the immune system, and be responsible for resistance to treatment.

Keywords: 5-HETE; 5-lipoxygenase; PUFA; arachidonic acid; cyclooxygenase-2; fatty acid; glioblastoma multiforme; leukotriene; prostaglandin.

Publication types

Review

Grants and funding

This study was supported by the statutory budget of the Department of Biochemistry and Medical Chemistry at Pomeranian Medical University in Szczecin, Poland and the Institute of Biology, University of Szczecin, Poland.