Apigenin-7-glucoside induces apoptosis and ROS accumulation in lung cancer cells, and inhibits PI3K/Akt/mTOR pathway

Abstract

Purpose: To investigate how apigenin-7-glucoside (AGL) affects the proliferation, migration, invasion, and reactive oxygen species (ROS) accumulation in lung cancer cells, and to evaluate the potential of AGL as a therapeutic target.
 Methods: Human bronchial epithelial cells (BEAS-2B), human lung carcinoma (A549), and non-small cell lung cancer cells (H1975), were treated with 25, 50, 100, and 200 μM AGL. Cell viability curves and EdU assays were used to evaluate their proliferation, while apoptosis was assessed by flow cytometry. Cell migration and invasion were evaluated by Transwell assays, and western blot was performed to determine the expression level of cytochrome C and phosphorylation of PI3K, AKT, and mTOR. Furthermore, ELISA was used to quantify the level of malondialdehyde (MDA) and glutathione (GSH). Indirect immunofluorescent assay (IFA) was performed by staining with DCFH-DA to evaluate ROS level.
 Results: Proliferation of A549 and H1975 cells was suppressed by AGL in a dose-dependent manner. AGL significantly reduced proliferation, promoted cell apoptosis, and attenuated the migration and invasion of A549 or H1975 cells. It also elevated the levels of cytochrome C and MDA but reduced the production of GSH in A549 and H1975 cells. AGL enhanced the accumulation of ROS and weakened phosphorylation of AKT, PI3K, and mTOR in A549 and H1975 cells.
 Conclusion: AGL represses proliferation, promotes apoptosis, suppresses migration and invasion, and induces ROS accumulation in lung cancer cells by repressing PI3K/Akt/mTOR pathway, thus indicating the potential of AGL as a target in lung cancer treatment.