Sanguisorba officinalis L. suppresses non-small cell lung cancer via downregulating the PI3K/AKT/mTOR signaling pathway based on network pharmacology and experimental investigation

Abstract

Background: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Sanguisorba officinalis L. (SOL), a traditional Chinese herbal medicine called Diyu, has been shown to have potent antitumor effects. However, the role of SOL in suppressing NSCLC remains unknown.Methods: Network pharmacology was employed for acquiring the potential targets and mechanisms of SOL in NSCLC. Based on the predictions of network pharmacology, we used CCK8 and EdU assays to investigate cell proliferation, flow cytometry to investigate apoptosis, wound healing assay to investigate cell migration, and transwell assay to investigate cell invasion in vitro. Western blot was employed for detecting the potential proteins, including signaling pathways and apoptosis. The A549-bearing athymic nude mice were employed to verify the effect on cell proliferation and apoptosis in vivo.Results: SOL significantly inhibited the proliferation, migration and invasion of NSCLC cells in a dose-dependent manner. Flow cytometry showed that the apoptotic ratio and ROS level of NSCLC cells increased significantly with increasing concentrations. AKT and the PI3K-AKT signaling pathway were analyzed as the most relevant target and pathway via network pharmacology predictions. Western blotting revealed that the expression levels of p-PI3K, p-AKT, and p-mTOR in NSCLC cells treated with SOL were significantly downregulated, while cleaved PARP-1 and caspase-3 were upregulated in a dose-dependent manner. The results in the mouse xenograft model were consistent with those in NSCLC cell lines.Conclusion: SOL downregulated the PI3K/AKT/mTOR signaling pathway to suppress NSCLC.

Suppressing inflammatory signals and apoptosis-linked sphingolipid metabolism underlies therapeutic potential of Qing-Jin-Hua-Tan decoction against chronic obstructive pulmonary disease

“…Animal experiments in the present study were authorized by the Center for Experimental Animal of Southwest Medical University, and all experimental procedures were approved by the Ethics Committee of Southwest Medical University [ 13 ] (license No. 20180309091).…”

Ginkgetin exhibits antifibrotic effects by inducing hepatic stellate cell apoptosis via STAT1 activation

“…Ginkgetin is a bioflavonoid extracted from Ginkgo biloba leaves, which exhibits a variety of bioactivities, such as anti‐inflammatory, antitumor, neuroprotective, and antioxidant properties (Adnan et al, 2020; Baek et al, 2016; Pan et al, 2019; Zhang et al, 2017). Mechanistic studies have revealed that ginkgetin induces cell autophagy and apoptosis and inhibits Wnt/β‐catenin, JAK2/STAT3, NFκB/P53, and Nrf2/HO‐1 signaling pathways (Liu et al, 2023; Lou et al, 2021; Pan et al, 2019; Wu et al, 2023). According to the pathogenesis of liver fibrosis and HSC activation, we hypothesized that ginkgetin may have antifibrotic potential.…”

“…Mechanistic studies have revealed that ginkgetin induces cell autophagy and apoptosis and inhibits Wnt/β-catenin, JAK2/STAT3, NFκB/ P53, and Nrf2/HO-1 signaling pathways (Liu et al, 2023;Lou et al, 2021;Pan et al, 2019;Wu et al, 2023). According to the pathogenesis of liver fibrosis and HSC activation, we hypothesized that ginkgetin may have antifibrotic potential.…”

Lnc-CLSTN2-1:1 Promotes Osteosarcoma Progression by Disrupting Redox Balance through PI3K/AKT Signaling Pathway

“…Maintaining the cellular redox balance is dependent on the balance between ROS generation and ROS consumption by antioxidant systems (e.g., GPx and TrxR) [29][30][31][32]. ROS is a double-edged sword; at low concentrations, ROS may function as a pro-tumorigenic signaling molecule, while at high ROS concentrations, it may act as a signaling molecule due to its deleterious, genotoxic, and even pro-apoptotic effects on cancer cells and may act as a cancer regulator [33][34][35][36]. LncRNAs play a role in regulating redox homeostasis in cancer cells by coordinating ROS [37].…”