Arachidonic Acid Pathway in Cancer Prevention

  • G. J. Kelloff
  • C. C. Sigman
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 156)


The potential role of products of arachidonic acid (AA) metabolism in carcinogenesis has been reviewed extensively (Kelloff et al. 1994; Marnett 1995; Taketo 1998a,b; Dannenberg et al. 2001; Funk 2001), as have cancer prevention strategies based on modulation of these pathways (Lippman et al. 1998; Kelloff 2000; Gupta and Dubois 2001; Anderson et al. 2002). AA metabolism begins with the intracellular release of AA, mediated by either phospholipase A2 (PLA2), or by the combined actions of phospholipase C (PLC) and diacylglycerol kinase or phospholipase D (PLD) and PLA2 (Needleman et al. 1986). In leukocytes, cytokines including IL-1 and TNF can activate PLA2 by stimulating a phospholipase-activating protein (Clark et al. 1991). AA is then metabolized to prostaglandins (PGs), thromboxanes, leukotrienes (LTs), and hydroxyeicosatetraenoic acids (HETEs) via oxidative enzymes (Funk 2001). Activated oxygen species and alkylperoxy species are formed throughout this process; AA metabolism is increased during inflammation. The major pathways of AA metabolism, PG synthesis and LT synthesis, are associated strongly with carcinogenesis; both are inhibited by antioxidants and anti-inflammatory agents. Evidence also suggests that direct modulation of cellular AA levels may affect carcinogenesis.


Colon Carcinogenesis Oral Premalignant Lesion Arachidonic Acid Pathway Flap Inhibitor Cancer Preventive Intervention 
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© Springer-Verlag Berlin Heidelberg 2003

Authors and Affiliations

  • G. J. Kelloff
  • C. C. Sigman

There are no affiliations available

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