The effect of quercetin on cell cycle progression and growth of human gastric cancer cells

Abstract

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...

Inhibitory effect of quercetin on OVCA 433 cells and presence of type II oestrogen binding sites in primary ovarian tumours and cultured cells

“…This observation is in agreement with previous studies on human gastric cancer (Yoshida et al, 1990) and IM 9 lymphoblastoid cells (unpublished observation). Interestingly, primary ovarian tumours express appreciable amounts of type II EBS.…”

“…Our data indicate that the flavonoid Q inhibits the growth of human ovarian cancer cells. This finding is in agreement with previous studies showing that Q has an antiproliferative action against human cancer cells in vitro (Markaverich et al, 1988;Yoshida et al, 1990). The observation that a dietary supplement of Q inhibits the development of 7,12-dimethylbenzanthracene and N-nitrosomethylurea induced rat mammary cancer (Verma et al, 1988) strongly support the possibility that Q could also be active in vivo.…”

Quercetin induces protective autophagy in gastric cancer cells: Involvement of Akt-mTOR- and hypoxia-induced factor 1α-mediated signaling

“…38 Consistent with previous reports, our study showed that quercetin inhibited proliferation and induced apoptosis in gastric cancer cells. 9 Autophagy is an evolutionary conserved, dynamic and lysosome-mediated process that involves the sequestration and delivery of cytoplasmic material to the lysosome where it is degraded and recycled. 39,40 Accumulating anticancer agents have been documented to trigger the cellular autophagic process, but the role that autophagy plays in cancer chemotherapy is still controversial.…”

“…attracted much attention in relation to its anticancer activities in many cancer cell models, including lymphoma, ovary, endometrial, prostate, liver and gastric cancer; [6][7][8][9] however, the molecular mechanisms underlying quercetin-mediated cellular responses remain poorly defined.…”

Isoflavones inhibit intestinal epithelial cell proliferation and induce apoptosis in vitro

“…Urinary phyto-oestrogen levels are also decreased in women with breast cancer (Ingram et al, 1997). Soyabean diets and individual isoflavones have also been shown to offer protection against mammary tumour development in animal models of cancer (Troll et al, 1980;Lamartiniere et al, 1995) and the related, naturally occurring flavone, quercetin, has been shown to decrease the growth of gastric cancer cells (Yoshida et al, 1990). It is likely that several anticancer mechanisms are involved in the protection offered by dietary isoflavones, examples that we have shown here are that apoptosis, oestrogenicity and tyrosine kinase inhibition may play a role.…”