What are cyclooxygenases and lipoxygenases doing in the driver's seat of carcinogenesis?
Substantial evidence supports a functional role for cyclooxygenase- and lipoxygenase-catalyzed arachidonic and linoleic acid metabolism in cancer development. Genetic intervention studies firmly established cause-effect relations for cyclooxygenase-2, but cyclooxygenase-1 may also be involved. In addition, pharmacologic cyclooxygenase inhibition was found to suppress carcinogenesis in both experimental mouse models and several cancers in humans. Arachidonic acid-derived eicosanoid or linoleic acid-derived hydro[peroxy]fatty acid signaling are likely to be involved impacting fundamental biologic phenomena as diverse as cell growth, cell survival, angiogenesis, cell invasion, metastatic potential and immunomodulation. However, long chain unsaturated fatty acid oxidation reactions indicate antipodal functions of distinct lipoxygenase isoforms in carcinogenesis, i.e., the 5- and platelet-type 12-lipoxygenase exhibit procarcinogenic activities, while 15-lipoxygenase-1 and 15-lipoxygenase-2 may suppress carcinogenesis.
Fürstenberger
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G
Research Group Eicosanoids and Tumor Development, Deutsches Krebsforschungszentrum Heidelberg, D-69120 Heidelberg, Germany. g.fuerstenberger@dkfz.de
Krieg
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Müller-Decker
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Habenicht
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AJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001091:Arachidonate Lipoxygenases / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004537:Eicosanoic Acids / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes; D019787:Linoleic Acid / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008084:Lipoxygenase / Q000187:drug effects / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000201:enzymology* / Q000378:metabolism; D009389:Neovascularization, Pathologic; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction
D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D004537:Eicosanoic Acids; D007527:Isoenzymes; D008054:Lipid Peroxides; D016718:Arachidonic Acid; D019787:Linoleic Acid; D001091:Arachidonate Lipoxygenases; D008084:Lipoxygenase; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases