Research biomedical science

Studies of arachidonic acid metabolism in human monocytes and cancer cell lines

Prostagrandins and leukotriens are impotent lipid mediators in inflammatory diseases such as asthma, atherosclerosis and rheumatisms and they have also been suggested to be involved in progression of various cancer forms. The initial step in the formation of these lipid mediators is a phospholipase A₂ (PLA₂) hydrolysis of membrane phospholipids generating arachidonic acid which is metabolised by either cyclooxygenas or lipoxygenase to generate prostaglandins and leukotriens respectively. Some of the effects mediated by prostaglandin are vasodilatation and modulation of the cytokine release and examples of effects of leukotriens are increase in vasopermeability and chemotaxis. Regarding tumor cells both prostaglandins and leukotriens have been suggested to promote proliferation of the cells.

PLA₂ consists of a superfamily of enzymes, however, which isoform of PLA₂ that is responsible for mobilization of arachidonic acid as well as the signaling pathways leading to activation of the enzymes is not fully understood. Furthermore the role of the constitutively expressed cyclooxygenase 1 versus the inducible form cyclooxygenas 2 and the terminal synthases involved in the formation of prostaglandins is also incomplete.

The signal transduction pathways, as well as direct measurement of the activity of enzymes involved in mobilisation of arachidonic acid, is investigated in human monocytes and cancer cell lines. In addition to known inhibitors of arachidonic acid metabolism the effects of compounds found in fruits and berries, such as different flavonoids and polyphenols, are also investigated.

Jonny Wijkander, Ass professor