Quercetin-induced apoptosis in colorectal tumor cells: Possible role of EGF receptor signaling

Flavanoids are among the best candidates for mediating the protective effec t of diets rich in fruits and vegetables with respect to colorectal cancer. To gain additional information about their growth effects on colorectal tu mors and their cellular mechanisms of action a series of related flavonoids was added to cultures of colonic turner cells. Most compounds induced grow th inhibition and cell loss at concentrations of 1-100 mu M, relative effec tivity being quercetin > apigenin > fisetin > robinetin and kaempferol. Myr icetin was only slightly effective. Quercetin was the strongest inducer of apoptosis in a process that was reversible until 10 hours by flavonoid remo val and until 24 hours by fetal calf serum. Cells were preferentially retai ned in the S phase. On the cellular level, quercetin sensitivity was correl ated with epidermal growth factor (EGF) receptor levels, rapid growth, and poor differentiation indicating the possibility of targeting those cells mo st harmful far the organism. The flavonoid transiently inhibited EGF recept or phosphorylation but had only little effect an other signaling molecules. Even after recovery, of receptor phosphorylation, cells remained resistant to EGF stimulation. In summary, the data indicate that inhibition of EGF r eceptor kinase is an integral part of quercetin-induced growth inhibition, but additional mechanisms also contribute to the overall effect.