#A200 Effect of Dietary Flavonoids on Oral Cancer Cell Proliferation: Bioactivation by Saliva and Antiproliferative Mechanisms. Thomas Walle, Teresita Alston, Alyson Browning, Susan Reed, U. Kristina Walle, Medical Univ. of South Carolina, Charleston, SC. Oral squamous epithelial cell cancer responds poorly to treatment. It may therefore benefit from chemopreventive strategies, e.g. inhibition of early neoplastic growth. Although dietary interventions have not received much attention in oral cancer, epidemiological studies suggest that this could be an important protective factor. In this study we focus on dietary flavonoids. In the first part of this study we show that quercetin-4’-O-glucoside (QG), one of the most abundant flavonoids in the human diet, is effectively hydrolyzed by human saliva to the more bioactive aglycone form quercetin (Q). This rapid hydrolysis appears to be related to â-glucosidase(s) expressed by the oral bacterial flora and was effectively inhibited by the oral antibacterials chlorhexidine and Listerine®. A preliminary population study demonstrates a 50-fold interindividual variability in this rate of hydrolysis. In the second part of this study, we used the oral squamous epithelial cancer cells SCC-9 (tongue), SCC-25 (tongue) and FaDu (pharynx) to determine the antiproliferative effects of Q and other flavonoids as well as their glycosides, using the MTT assay, which determines the number of viable cells. Q as well as apigenin and genistein inhibited SCC-9 cell proliferation in a concentration-dependent manner with a minimum effective concentration of about 5-10 ́M (P < 0.05), concentrations easily achieved in the oral cavity after common diets. Although these flavonoids were also proapoptotic, using the TUNEL assay, this effect occurred at higher concentrations. In sharp contrast, several flavonoid glycosides had no effect in the MTT assay. In the third part of this study we have started to explore the mechanism(s) of the antiproliferative effects, initially focusing on Q. Q was shown to enter the SCC-9 cells readily, was then oxidized by reactive oxygen species and covalently bonded to specific proteins. When submitting SCC-9 cell lysate to SDS-PAGE with autoradiography two of the major radiolabeled proteins, at about 55 and 85 kDa, may be regulatory adapter subunits of PI3-kinase. Thus, dietary QG and other flavonoid glycosides are hydrolyzed by â-glucosidase(s) in the saliva, liberating the more active aglycones in the oral cavity to potentially inhibit oral cancer cell proliferation via interactions with specific signaling proteins. Supported by a Hollings Cancer Center Department of Defense grant and the National Institutes of Health grant GM55561. Frontiers in Cancer Prevention Research, 2003 AACR Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.