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What are cyclooxygenases and lipoxygenases doing in the driver's seat of carcinogenesis?
Author(s) -
Fürstenberger G.,
Krieg P.,
MüllerDecker K.,
Habenicht A.J.R.
Publication year - 2006
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22153
Subject(s) - arachidonic acid , lipoxygenase , eicosanoid , carcinogenesis , cyclooxygenase , linoleic acid , arachidonate 5 lipoxygenase , angiogenesis , biochemistry , biology , chemistry , fatty acid , cancer research , enzyme , gene
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 phenomina 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. © 2006 Wiley‐Liss, Inc.