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Effects of protolichesterinic acid, a lichen compound, on the ERK1/ERK2 signalling pathway in cancer cells and normal endothelial cells
The lichen metabolite protolichesterinic acid (PA) has been found to be a potent inhibitor of 5- and 12-lipoxygenase as well as having anti-proliferative effects on several types of cancer cells[1,2,3]. ERK1/ERK2 is a major regulator of cell cycle progression and can be activated e.g. through growth factor stimulation or by constitutive Ras activation which is common in many cancers. The aim of this study was to isolate pure PA and investigate its effect on ERK signalling pathway in pancreatic cancer cells (PANC-1), multiple myeloma cells (U266, RPMI-8226) and normal human umbilical vein endothelial cells (HUVEC). The lichen material was extracted with petroleum ether, re-crystallized in methanol and further purified using preparative RP-HPLC. 1H and 13C NMR was used to characterize the structure of PA. Activation of ERK1/2 was detected by Western blotting using specific antibodies for the phosphorylated form. Results show that PA has an inhibitory effect on ERK activation in HUVEC cells at the concentration of 5µg/mL. PANC-1 cells were not affected. Preliminary results indicate that PA may be inhibitory in myeloma cells. Different effects on different cell lines may reflect different pathways towards ERK activation, only some of which are influenced by PA. The effects on endothelial cells are interesting in terms of potential anti-angiogenic activity.
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