Open AccessNaringin induces apoptosis of gastric carcinoma cells via blocking the PI3K/AKT pathway and activating pro‑death autophagy
Author(s) -
Cuixiang Xu,
Xiaoyan Huang,
Huang Ya,
Xiao Liu,
Min Wu,
Jianhua Wang,
Xianglong Duan
Publication year - 2021
Publication title -
molecular medicine reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.727
H-Index - 56
eISSN - 1791-3004
pISSN - 1791-2997
DOI - 10.3892/mmr.2021.12412
Subject(s) - autophagy , apoptosis , pi3k/akt/mtor pathway , cell cycle , protein kinase b , microbiology and biotechnology , cell growth , flow cytometry , biology , cell , cancer cell , programmed cell death , chemistry , signal transduction , cancer research , cancer , biochemistry , genetics
Naringin (Nar) is one of the natural glycosides extracted from pomelo and other citrus fruits. It has various pharmacological activities, including anti‑inflammatory, antioxidant, anti‑proliferative and anti‑cancer. However, the underlying mechanisms by which Nar regulates apoptosis and autophagy in gastric cancer remain unclear. Thus, the present study aimed to assess the therapeutic effect of Nar and the underlying mechanisms. SNU‑1 cell proliferation was determined using Cell Counting Kit‑8 assay. Cell morphological changes were observed under a phase‑contrast microscope. The changes in the cell cycle were determined using flow cytometry analysis and the changes in cell apoptosis were determined using flow cytometry, Hoechst 33258 and TUNEL staining. The protein levels pertaining to the PI3K/AKT pathway and cell apoptosis and autophagy were monitored using western blot analysis. The results demonstrated that Nar significantly inhibited SNU‑1 cell growth and induced cell cycle arrest in the G0/G1 phase and cell apoptosis. Further mechanistic studies demonstrated that Nar blocked the PI3K/AKT pathway, activated cell autophagy and stimulated the expression of apoptosis‑associated protein cleaved caspase 3 and Bax, but decreased the expression of Bcl‑2. Preincubating SNU‑1 cells with 3‑methyladenine, a cell‑autophagy inhibitor, significantly alleviated the effects of Nar in promoting cell apoptosis and cleaved caspase 3 expression. It was concluded that Nar promoted SNU‑1 cell apoptosis via blocking the PI3K/AKT signaling pathway and activating cell autophagy.