genistin and Mouth-Neoplasms

Increasing epidemiological evidence supports the view that dietary flavonoids have protective roles in oral diseases, including cancer. However, the dietary forms of flavonoids, the flavonoid glycosides, must first be hydrolyzed to the aglycones, which is thought to occur mainly in the intestine. In the present study we tested whether this hydrolytic activity occurs in the oral cavity. Saliva was collected from human subjects, incubated with flavonoid glycosides, and analyzed for aglycone formation by HPLC. When quercetin 4'-glucoside or genistein 7-glucoside was incubated with human saliva, hydrolysis to quercetin and genistein, respectively, was detected within minutes. Studies of additional flavonoid glycosides demonstrated that glucose conjugates were rapidly hydrolyzed, but not conjugates with other sugars, i.e., rutin, quercitrin, and naringin. In a limited study of 17 subjects, the interindividual variability in the hydrolysis of genistein 7-glucoside was >20-fold. This supports the contention that salivary hydrolysis of certain flavonoid glucosides may be important in some individuals but not in others. Support for a bacterial contribution to this hydrolysis was obtained from the inhibitory effect of antibacterials in vivo and in vitro and from experiments with subcultured oral bacterial colonies. However, cytosol isolated from oral epithelial cells was also capable of effective hydrolysis. Dietary flavonoid glucosides may thus be hydrolyzed in the oral cavity by both bacteria and shedded epithelial cells to deliver the biologically active aglycones at the surface of the epithelial cells. The aglycones quercetin and genistein both potently inhibited proliferation of oral cancer cells. The large interindividual variability in this hydrolytic activity may be a factor that should be taken into consideration in future studies.

Topics: Antineoplastic Agents; Carcinoma, Squamous Cell; Cell Division; Cell Line, Tumor; Flavanones; Flavonoids; Glucosides; Humans; Hydrolysis; Isoflavones; Mouth Neoplasms; Saliva

Epidemiologic evidence supports the view that dietary flavonoids exert protective effects in oral diseases, including cancer. However, the dietary forms of flavonoids, the flavonoid glycosides, are thought to be inactive, thus they must first be hydrolysed to their active aglycones. This may occur in the saliva in the oral cavity. We have examined if the flavonoid glycosides directly could affect cell proliferation, using the human oral squamous carcinoma SCC-9 cells. The cellular uptake and hydrolysis of the glycosides were assessed also. The four flavonoid glycosides tested each behaved differently. Genistin, the 7-glucoside of genistein, showed clear and consistent inhibition of cell proliferation, which appeared to be the result of rapid cellular uptake of the glucoside and hydrolysis to genistein. Spiraeoside, the 4'-glucoside of quercetin, showed a similar inhibition of cell proliferation, which also appeared to be associated with its hydrolysis to quercetin. Diosmin, the 7-rutinoside of diosmetin, surprisingly, was more potent and effective than diosmetin. In contrast, quercitrin, the 3-rhamnoside of quercetin, showed no effect and only minimal cellular uptake and no hydrolysis. In summary, dietary flavonoid glycosides may exert cellular effects in the oral cavity, but this varies greatly with the nature of the glycoside.

Topics: Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Diet; Diosmin; Dose-Response Relationship, Drug; Flavonoids; Glycosides; Humans; Hydrolysis; Isoflavones; Mouth Neoplasms; Quercetin