Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Gastric cancer cell proliferation is inhibited by &alpha-santonin via targeting of PI3K and AKT activation

Lin Nie, Lijiu Zhang

Department of Gastroenterology, The Second Hospital of Anhui Medical University, Hefei City, Anhui Province 230601, China;

For correspondence:- Lijiu Zhang Email: xiyangone@sina.com Tel:+8613956976104

Accepted: 24 January 2020 Published: 30 April 2020

Citation: Nie L, Zhang L. Gastric cancer cell proliferation is inhibited by &alpha-santonin via targeting of PI3K and AKT activation. Trop J Pharm Res 2020; 19(4):765-771 doi: 10.4314/tjpr.v19i4.13

© 2020 The authors.
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Abstract

Purpose: To investigate the effect of α-santonin on proliferation of gastric cancer cells.

Methods: Cell proliferation was analysed by 3Ã¢â‚¬â€˜4Ã¢â‚¬â€˜5Ã¢â‚¬â€˜DimethylthiazolÃ¢â‚¬â€˜2Ã¢â‚¬â€˜ylÃ¢â‚¬â€˜25Ã¢â‚¬â€˜diphenyltetrazolium bromide (MTT) assay and migration by wound healing assay. Matrigel coated Transwell chamber was used for determination of cell invasion. expression of proteins and mRNA was assessed using western blot and RT-PCR assay, respectively.

Results: In NUGC4 and MKN45 cell cultures, treatment with α-santonin promoted miR 145 expression significantly when compared to control. Treatment of NUGC4 cells with α-santonin for 48 h significantly increased apoptosis in comparison to control. At 100, 150 and 200 µM concentrations of α-santonin, the level of cell apoptosis increased to 45, 53 and 64 %, respectively (p < 0.05). Treatment with α-santonin caused NUGC4 cell population increase in G1/G0 phase with reduction in S and G2/M phases. A significant reduction in NUGC4 cell invasion was observed following treatment with α-santonin. The α-santonin treatment of NUGC4 cells at 200 µM concentration markedly reduced cell invasion (p < 0.05). Treatment of NUGC4 cells with α-santonin reduced the expression of c Myc, PI3K, and p AKT. The production of MMP-2 and MMP-9 in NUGC4 cells was also decreased by α-santonin treatment.

Conclusion: The study demonstrates that α-santonin plays important role in inhibition of gastric cancer cell proliferation by arrest of cell cycle and apoptosis induction. Moreover, the activation of PI3K and AKT was also suppressed by α-santonin. Therefore, α-santonin can potentially be used for the treatment of gastric cancer.

Keywords: Apoptosis, MicroRNA, Tumor suppressor, Metastasis, Infiltration