Effects of the flavonoid luteolin on Cox-2 and PGE2 expression in RAW 264.7 cells

4737 Flavonoids are ubiquitous plant compounds that have recently been scrutinized for anti-cancer effects. Luteolin, a flavonoid found in rosemary, celery, and other edible plants, has been shown to inhibit multiple cancer-related signal transduction pathways, including MAPK, NFκB, and Akt. Conversely, the effects of luteolin on Cox-2 signalling have not been reported. RAW 264.7 cells were pre-treated for 2 hours with 100, 50, 25, 10, or 5 μM luteolin, then treated with LPS (1 μg/ml) for an additional 12 hours. Pre-treatment of RAW 264.7 cells with luteolin inhibited Cox-2 protein expression, measured by Western blot, in a dose-dependent manner. Similarly, PGE2 expression, measured by ELISA, was reduced in a dose-dependent manner. Intracellular hydrogen peroxide production, measured microscopically with a DCFDA fluorescent probe, was also reduced in luteolin pre-treated cells. Cell viability (MTT assay) was unaffected by dose. However, cell morphology, as viewed by confocal microscopy, was dramatically affected. This study indicates that luteolin pretreatment reduces Cox-2 expression and PGE2 formation. Furthermore, the effects of luteolin are not due to toxicity, and may be related to an inhibition of reactive oxygen species or effects on genes controlling cell morphology.