Abstract
Oxylipins derived from the oxidation of polyunsaturated fatty acids (PUFAs) act as important paracrine and autocrine signaling molecules. A subclass of oxylipins, the eicosanoids, have a broad range of physiological outcomes in inflammation, the immune response, cardiovascular homeostasis, and cell growth regulation. Consequently, eicosanoids are implicated in the pathophysiology of various diseases, most notably cancer, where eicosanoid mediated signaling is involved in tumor development, progression, and angiogenesis. Cytochrome P450s (CYPs) are a superfamily of heme monooxygenases generally involved in the clearance of xenobiotics while a subset of isozymes oxidize PUFAs to eicosanoids. Several eicosanoid forming CYPs are overexpressed in tumors, elevating eicosanoid levels and suggesting a key function in tumorigenesis and progression of tumors in the lung, breast, prostate, and kidney. This review summarizes the current understanding of CYPs' involvement in solid tumor etiology and progression providing supporting public data for gene expression from The Cancer Genome Atlas.
Highlights
Eicosanoids are a subset of physiologically active oxylipins derived from arachidonic acid (AA) oxidation
Elevated epoxyeicosatrienoic acids (EETs) levels in patients are linked to higher CYP2C and CYP2J2 mRNA and protein expression in tumor cells compared to adjacent normal cells (Wei et al, 2014; Apaya et al, 2019)
While this study provides some experimental evidence that EETs and 20-hydroxyeicosatetraenoic acids (HETEs) have significant roles in prostate cancer as pro-angiogenic factors, it is important to note that the investigators measured mRNA levels of these enzymes, both epoxygenases and hydroxylases, but did not measure protein expression or eicosanoids
Summary
Eicosanoids are a subset of physiologically active oxylipins derived from arachidonic acid (AA) oxidation. Elevated EET levels in patients are linked to higher CYP2C and CYP2J2 mRNA and protein expression in tumor cells compared to adjacent normal cells (Wei et al, 2014; Apaya et al, 2019). In addition to elevated CYP epoxygenase expression, studies show reduced levels of soluble epoxide hydrolase (sEH), the enzyme responsible for the hydrolysis of EETs to the dihydroxyeicosatrienoic acids (DHETs), depicted in Scheme 1 (Wei et al, 2014).
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