Targeting the enzymes involved in arachidonic acid metabolism to improve radiotherapy

Abstract

During radiotherapy, an inflammatory response might be induced by activating various enzymes involved in membrane lipid metabolism. The eicosanoid pathway associated with cytosolic phospholipase A2 (cPLA₂), cyclooxygenases (COXs), and lipoxygenases (LOXs) can be induced by radiation, and many lipid metabolites might contribute to cancer-associated inflammation, cell proliferation, and cell survival in cancer. The lipid metabolites are also involved in the establishment of the tumor-associated microenvironment through promotion of angiogenesis and formation of vascular network. These biological activities of lipid metabolites are responsible for malignant progression with the acquisition of radioresistance, leading to unsatisfactory outcome of cancer radiotherapy. Many efforts have been made to identify the mechanisms associated with bioactive lipid metabolites and radiation signaling that lead to radioresistance and to develop potent radiosensitizers to improve therapeutic efficacy. Beneficial outcomes would be achieved by targeting the enzymes, such as cPLA₂, COXs, and LOXs, responsible for arachidonic acid metabolism and cancer-associated inflammation during cancer radiotherapy. The current study demonstrated a brief review for the radioresistant effects of bioactive lipid metabolites and their enzymes in cancer and the radiosensitizing effects of inhibitors for the enzymes on cancer therapy.

Keywords: Arachidonic acid; Cyclooxygenase; Cytosolic phospholipase A2; Lipoxygenase; Radioresistance.