Anti-apoptotic effects of silver nanoparticles green-formulated by Phellodendron amurense leaf extract on NCI-H661 human lung adenocarcinoma cell line and following the PI3K/AKT/mTOR signaling pathway and its application for A3 coupling reaction

Abstract

Because plant extracts are simple, environmentally benign, and physiologically safe alternatives to chemical processes, there is increasing interest in employing them for the biogenic manufacture of silver nanoparticles (Ag NPs). The current research described a cost-efficient and eco-friendly approach for the Ag NPs green synthesis from AgNO₃ using an aqueous extract of Phellodendron amurense leaves as a reducing agent. The phenolics hydroxyl functional groups in P. amurense leaf extract act as capping/stabilizing and reducing agents. The Ag NPs/P. amurense nanocomposite was characterized using techniques such as UV-Vis, TEM, SEM, EDX, ICP-OES, and XRD. Results from SEM and TEM revealed that the generated silver nanoparticles had a spherical shape structure and their size was around 20 to 30 nm. NCI-H661 human lung adenocarcinoma cell line was used to evaluate the biogenic Ag NPs/P. amurense nanocomposite anti-lung cancer capabilities. The MTT experiment showed that the Ag NPs/P. amurense nanocomposite could strongly inhibit the proliferation of NCI-H661 human lung adenocarcinoma cells. Without causing any damage to the normal cell line, Ag NPs/P. amurense nanocomposite demonstrated extremely poor cell survival and dose-dependent anti-human lung cancer effects. The Ag NPs/P. amurense nanocomposite' IC₅₀ value against the NCI-H661 cell line was 147 µg/ml. Through a detailed examination of the Phosphatidylinositol 3-Kinase (PI3K)/Protein Kinase B (Akt)/Mammalian Target of Rapamycin (mTOR) pathway, it was observed that Ag NPs/P. amurense nanocomposite can alter the PI3K/AKT/mTOR pathway, affecting NCI-H661 human lung adenocarcinoma cells cell growth and death. This pathway may contribute to the cell cycle inhibition and apoptosis induction by Ag NPs/P. amurense nanocomposite. Our data suggest that Ag NPs/P. amurense nanocomposite might be a very promising anticancer drug against human lung adenocarcinoma cells. The catalytic performance of the Ag NPs/P. amurense was investigated for the generation of propargylamines derivatives through a three-component reaction involving amines, alkynes, and aldehydes (A³ coupling). The Ag NPs/P. amurense catalyst was exhibited sufficient recyclability until 6 successive cycles without significant activity loss.