The Arachidonic Acid Pathway and its Role in Prostate Cancer Development and Progression

Purpose

The arachidonic acid pathway incorporates phospholipase, cyclooxygenase, lipoxygenase and epoxygenase enzymes. This pathway has been shown to have a major role in the development and progression of a number of cancers, including prostate cancer. We discuss the current status of research of this pathway in the area of prostate cancer, ranging from preclinical in vitro studies to human clinical trials.

Materials and Methods

We performed an online search of the current and past peer reviewed literature on prostate cancer and arachidonic acid, phospholipase, cyclooxygenase, lipoxygenase, epoxygenase, platelet activating factor, prostaglandin and eicosanoid. We retrieved and evaluated all full-length articles published in English from the 1980s to January 2007.

Results

Epidemiological evidence suggested that nonsteroidal anti-inflammatory drugs may decrease the risk of prostate cancer. This effect, presumably through the inhibition of cyclooxygenase-2, has been validated in preclinical studies. Cyclooxygenase-2 inhibition has also decreased the rate of prostate specific antigen increase in men with biochemical recurrence after treatment for prostate cancer. Although lipoxygenase and secretory phospholipase A2 inhibition was also effective for decreasing prostate cancer growth in preclinical studies, to our knowledge these strategies have not yet been used in clinical trials. Cytosolic phospholipase A2, platelet activating factor and epoxygenase need further investigation to determine a role in prostate cancer.

Conclusions

Evolving data suggest a significant role for some areas of the arachidonic acid pathway in prostate cancer. Inhibiting 1 or a number of these enzymes in combination may hold promise for future prostate cancer treatment.

Key Words: prostate, prostatic neoplasms, arachidonic acid, prostaglandin-endoperoxide synthases, lipoxygenase

Abbreviations and Acronyms: AA, arachidonic acid, ANX, annexin, COX, cyclooxygenase, cPLA2, cytosolic PLA2, EET, epoxyeicosatrienoic epoxide, EOX, epoxygenase, HETE, hydroxyeicosatetraenoic acid, IHC, immunohistochemistry, LOX, lipoxygenase, lyso-PAF, 1-alkyl-2-lyso-n-glycero-phosphocholine, MAPK, mitogen activated protein kinase, NSAID, nonsteroidal anti-inflammatory drug, PAF, platelet activating factor, PC, prostate cancer, PG, prostaglandin, PIN, prostatic intraepithelial neoplasia, PLA2, phospholipase A2, PSA, prostate specific antigen, RT-PCR, reverse transcriptase-polymerase chain reaction, sPLA2, secreted PLA2, WB, Western blot