12-Lipoxygenase: classification, possible therapeutic benefits from inhibition, and inhibitors

The metabolism of arachidonic acid can be catalyzed by either one of two enzyme families; the cyclooxygenases or the lipoxygenases. The family of lipoxygenases is divided into four subtypes according to tissue distribution; 5-, 8-, 12-, and 15-lipoxygenase. 12-lipoxygenase metabolites, such as 12(S)-hydroxyeicosatetraenoic acid, have been found to play a central role in the various stages of the metastatic process in tumors and are, therefore, potential targets for anticancer treatment. A variety of lipoxygenase inhibitors already exist and can be classified into five major categories according to their mechanism of inhibition. These include antioxidants, iron chelators, substrate analogues, lipoxygenase-activating protein inhibitors, and, finally, epidermal growth factor-receptor inhibitors.