Abstract
Purpose: To determine the anti-proliferative potential of quinolinone against gastric cancer cells, and the underlying mechanism of action.Methods: Quinolinone-mediated proliferative changes were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, while its effect on apoptosis was determined by flow cytometry. Transwell and wound healing assays were used for the determination of the effect of quinolinone on cell invasion and migration. The effect of quinolinone on protein expression levels were assayed with western blotting.Results: Quinolinone caused reduction in gastric cancer cell viability, but it had no effect on normal (GES-1) cells. Treatment with 8 μM quinolinone reduced the viability of SNU-5 and SGC-7901 cells to 32 and 27 %, respectively. Moreover, 8 μM quinolinone induced 67.90 and 71.54 % apoptosis in SNU-5 and SGC-7901 cells, respectively. Quinolinone significantly increased the population of cells in G1 phase, and suppressed migration potential (p < 0.05). Furthermore, in quinolinone-treated cells, the expression levels of p-PI3K, c-Myc and p-AKT were much lower than those in untreated cells (p < 0.05). Quinolinone also downregulated the expressions of MMP-2 and MMP-9, while it upregulated p21 expression in SNU-5 and SGC-7901 cells.Conclusion: Quinolinone suppresses the growth of SNU-5 and SGC-7901 gastric cancer cells via cell cycle arrest, induction of apoptosis and downregulation of the expressions of c-Myc and metalloproteinases. Thus, quinolinone may be developed as a potential drug candidate for the treatment of gastric cancer.
 Keywords: Gastric cancer, Apoptosis, Metalloproteinases, Phosphorylation
Highlights
Gastric cancer, a life-threatening disease worldwide, has very poor prognosis [1,2]
The present study evaluated the anti-proliferative potential of quinolinone against gastric cancer cells, and the associated mechanism
The viability of SNU-5 cells decreased to 32 %, whereas that of SGC-7901 cells was reduced to 27 % on treatment with 8 μM quinolinone
Summary
A life-threatening disease worldwide, has very poor prognosis [1,2]. It has been reported that the incidence of gastric cancer is much higher in the developing nations of South America, East Asia and some European countries than in developed countries [3]. The staining was carried out for 20 min in the dark at room temperature for analysis of apoptosis using a flow cytometer (Cytomics FC 500; Beckman Coulter Inc., Miami, FL, USA). The SNU-5 and SGC-7901 cells were seeded separately, each at a density of 2 x 106 cells/well and treated with 8.0 μM quinolinone in 6-well plates for 48 h. The SNU-5 and SGC-7901 cells were seeded and treated with 8.0 μM quinolinone as described under apoptosis assay. Differences were taken as significant at p < 0.05
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