Lipoxygenase Inhibitors for Cancer Prevention: Promises and Risks

Author(s): Cecilia Menna , Fabiola Olivieri , Alfonso Catalano , Antonio Procopio .

Journal Name: Current Pharmaceutical Design

Volume 16 , Issue 6 , 2010

Abstract:

It is well established that an increase of n-6 polyunsaturated (i.e. arachidonic and arachidonic-converted linoleic acids) fat dietary intake enhances carcinogenesis and promotes tumorigenesis through oxidative metabolism. The Cyclooxygenase (COX) and Lipoxygenase (LOX) enzymes mediate the oxidative metabolism of n-6 polyunsaturated fatty acids and generate a cascade of biological active molecules. Nonsteroidal antinflammatory drugs (NSAIDs) modulating arachidonic acid (AA) metabolism have been utilized in cancer chemoprevention. The gastrolesivity of a prolonged use of nonselective NSAIDs, due to the COX inhibition, an important housekeeping gene of the gastrointestinal system, contraindicated their use in chemoprevention. Moreover, cardiovascular side effects emerged in the long-term use of COX-2 specific inhibitors rising doubts on their use for cancer chemoprevention. This evidence renewed the interest into other AA-metabolizing pathways relevant in inflammation and carcinogenesis. Here, the role of the LOXs pathways in carcinogenesis is reviewed. Inhibition of the LOX pathways, alone or in association with COX-2 pathway, appears to be a promising field for detecting new molecular target and engineering new chemopreventive strategies on cancer.

Keywords: Lipoxygenase inhibitors, cancer prevention, cellular senescence

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Article Details

VOLUME: 16
ISSUE: 6
Year: 2010
Page: [725 - 733]
Pages: 9
DOI: 10.2174/138161210790883822
Price: $58

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