Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Quinolinone inhibits proliferation of gastric cancer cells and induces their apoptosis via down-regulation of the expression of pro-oncogene c-Myc

Wenguang Liu¹, Jing Ma², Xinrui Chen³, Baoli Xu³

¹Department of Emergency Surgery, Linyi People's Hospital; ²Lanshan District Community Health Service Center; ³Department of General Surgery, Linyi People’s Hospital, Linyi, Shandong 276002, China.

For correspondence:- Baoli Xu Email: elf0909@126.com Tel:+865398211211

Accepted: 23 July 2020 Published: 31 August 2020

Citation: Liu W, Ma J, Chen X, Xu B. Quinolinone inhibits proliferation of gastric cancer cells and induces their apoptosis via down-regulation of the expression of pro-oncogene c-Myc. Trop J Pharm Res 2020; 19(8):1599-1604 doi: 10.4314/tjpr.v19i8.5

© 2020 The authors.
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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