Cyclooxygenases and lipoxygenases in cancer

Abstract

Cancer initiation and progression are multistep events that require cell proliferation, migration, extravasation to the blood or lymphatic vessels, arrest to the metastatic site, and ultimately secondary growth. Tumor cell functions at both primary or secondary sites are controlled by many different factors, including growth factors and their receptors, chemokines, nuclear receptors, cell–cell interactions, cell–matrix interactions, as well as oxygenated metabolites of arachidonic acid. The observation that cyclooxygenases and lipoxygenases and their arachidonic acid-derived eicosanoid products (prostanoids and HETEs) are expressed and produced by tumor cells, together with the finding that these enzymes can regulate cell growth, survival, migration, and invasion, has prompted investigators to analyze the roles of these enzymes in cancer progression. In this review, we focus on the contribution of cyclooxygenase- and lipoxygenase-derived eicosanoids to tumor cell function in vitro and in vivo and discuss hope and tribulations of targeting these enzymes for cancer prevention and treatment.

Structural and dynamic insights into substrate binding and catalysis of human lipocalin prostaglandin D synthase

“…3 In our crystal structure we observed the ligand density near Phe 83, Cys 65, and Ser 67. The aromatic ring of the conserved Phe 83 is positioned facing the cyclopentane ring of the modeled substrate analog in site A1 (as well as in site A2).…”

Role of phospholipases in adrenal steroidogenesis

“…5-HPETE can also be converted to leukotrienes. Eicosanoids are very important in inflammatory processes as well as proliferation and other cell responses (reviewed in Schneider & Pozzi 2011, Lone & Tasken 2013. In each case, these molecules appear to act locally (i.e., within a tissue) by binding to receptors on the plasma membrane; in other words, they act as ligands for G protein-coupled receptors.…”

Predicting Drug Targets and Biomarkers of Cancer via Genome-Scale Metabolic Modeling

“…Among them are polyamines, isoprenoid, prostaglandins, and leukotrienes. These metabolites are tightly linked to oxidative stress, prenylation of oncogenes, and inflammation, respectively (68)(69)(70). Indeed attempts have been made to treat cancer by reducing the level of these metabolites in the tumor through inhibition of their production or uptake (71)(72)(73).…”