Abstract
Mobilization of esterified arachidonic acid (AA) from membrane glycerolipid pools represents the key regulatory step in cellular responses to various stimuli, such as growth factors, cytokines, chemokines and circulating hormones. Released AA is metabolized via the cyclo-oxygenase (COX 1 and COX 2), lipoxygenase (LOX) or P450-dependent epoxygenase pathways to generate eicosanoids. In addition to their normal biological activities, such as stimulation of mitogenesis and cellular motility, eicosanoids have also been postulated to contribute to tumorigenesis and to the progression of certain tumor cells. Various AA metabolites have been implicated in a variety of growth-related signaling pathways involving ras (Han et al. 1991), interferon-α, epithelial growth factor (EGF), cyclic adenosine monophosphate, protein kinase C (PKC; Hannigan and Williams 1991; Peppelenbosch et al. 1993; Tang et al. 1995a), mitogen-activated kinases (Rao et al. 1988) and fos (Danesch et al. 1994). Numerous studies have demonstrated a strong correlation between growth-factor-promoted cell proliferation and generation of various COX products, primarily prostaglandins (Nolan et al. 1988).
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