Quercetin, a flavonoid, is found in many plants, including edible fruits and vegetables. We examined the effects on cell growth of human malignant cells derived from the gastrointestinal tract and on cell cycle progression. Quercetin markedly inhibited the growth of human gastric cancer cells and the ICsO value was 32-55 PM. DNA synthesis was suppressed to 14% of the control level by the treatment with 70 PM quercetin for 2 days.Furthermore, quercetin blocked cell progression from the Gi to the S phase.Quercetin; Cell cycle; (Human gastric cancer cell)
1, INTRODUCTIONQuercetin, a flavonoid found in many plants, is widely distributed in edible fruits and vegetables. Humans regularly consume foods containing quercetin not only in its free form, but also in the fi-glycoside form, such as rutin and quercitrin. When quercetin was administered orally, it was poorly absorbed from the digestive tract and did not have a great influence on the organs except the gastrointestinal tract. A proportion of the quercetin administered was degraded by the intestinal microflora and the remainder was excreted in feces in an unchanged form [l-2].Recently quercetin was found to inhibit the cell growth of leukemia cells, Ehrich ascites tumor cells [3], and NK/Ly ascites tumor cells 141. To clarify the mechanism of anti-tumor effects, we examined its effect on the cell growth of four human gastric cancer cell lines, as well as on the cell cycle.
MATERIALS AND METHODS
Cell line and chemicalsQuercetin was purchased from Wako Pure Chemical Industries, Osaka. In this study, four human gastric cancer cell lines, HGC-27 [S], NUGC-2 [6], were used. Ceils were cultured in RPM1 1640 (Nissui) supplemented with 10% fetal calf serum and incubated at 37°C in a humidifi~ atmosphere containing 5% COz. Quercetin was dissolved in 0.25% dimethy sulfoxide (DMSO) and diluted to its final concentration in each culture dish.
Measurement of cytotoxicityCells were plated at a density of 4 x 104 cells/2 ml medium in Correspondence address: M. Yoshida, Institute for Oriental Medicine, Hyogo, l-l-l, Higashidaimotsu-thou, Amagasaki 660, Japan 10 35 mm diameter dishes. The various concentrations of quercetin were added at the inoculation of cells, or at the 2nd day after the inoculation of cells. Control cells were exposed to DMSO at the same concentration as the other dishes. The culture was continued without medium change. The number of viable cells were measured by the Trypan blue dye exclusion test. The values represent means * SD. Data were analyzed using a two-tailed Student's t-test.
Me~urement of DNA synthesis. DNA synthesis was assayed at 1, 3, 12, 18, 24, 36, and 48 h after treatment with quercetin. HGC-27 cells were incubated for 1 h with 10,&i of ['H]thymidine. The cells were washed with 2 ml of phosphate-buffered saline, treated with 2 ml of 5% trichloroacetic acid (TCA), and kept overnight or longer in a wet chamber. Cells were washed with 2 ml of 5% TCA and solubilized with 0.8 ml of 1% sodium dodecyl sulphate. The radioactivities of aliquots were c...
