Comparison of the mechanisms of action of three cancer chemopreventive flavonoids
Tricin (4',5,7-trihydroxy-3',5 '-dimethoxyflavone) from grass species and apigenin (4 ',5,7-trihydroxyflavone) from leafy vegetables are chemically closely related flavones. Quercetin (3,5,7,3',4 '-pentahydroxyflavone) is a flavonol contained in onions, wine, French beans and apples. These flavonoids have been reported to inhibit the growth of a variety of human-derived malignant cells in vitro at microM concentrations. Tricin, apigenin and quercetin showed differential growth-modulating abilities when they were incubated with colon-derived cells. Apigenin and more growth-inhibitory than tricin and quercetin in SW480 and HCA-7 cells. Whilst apigenin at 40 microM induced moderate apoptosis in HCA-7 cells, it arrested the cell cycle of SW480 cells without induction of apoptosis. In contrast to tricin and quercetin, which inhibited activity of COX enzymes strongly in a cell free system and decreased cellular PGE-2 levels moderately in HCA-7 and HCEC cells, apigenin lacked COX enzyme-inhibitory activity in the cell-free system. However, it reduced cellular PGE-2 moderately in HCA-7 cells and dramatically in HCEC cells, but it did not down-regulate COX-2 expression. The effect of apigenin on PGE-2 levels suggests that it may target the PGE-2 signalling pathway without effect on COX activity and expression. It is conceivable that apigenin affects cellular PGE-2 levels by induction or stimulation of the PGE-2 metabolising enzyme 15-hydroxyprostaglandin dehydrogenase. The results suggest that the pharmacological profile of apigenin renders it perhaps a more attractive chemopreventive agent than tricin or quercetin. The further exploration of the cancer chemopreventive properties of apigenin in rodent model in vivo is required.