Exploring the anticancer effects of tin oxide nanoparticles synthesized by pulsed laser ablation technique against breast cancer cell line through downregulation of PI3K/AKT/mTOR signaling pathway

Abstract

Tin oxide nanoparticles (SnO2 NPs) demonstrate potential anti-cancer functions. However, the anti-cancer mechanisms of SnO2 NPs have not been explored in detail. In the present study, we synthesized SnO2 NPs through laser ablation technique and examined their anticancer mechanisms and the probable involvement of the PI3K/AKT mediated pathways in human breast cancer cells (MCF-7) in vitro. The synthesized SnO2 NPs were characterized by transmission electron microcopy (TEM), dynamic light scattering (DLS), and Fourier-transform infrared spectroscopy (FTIR) techniques. Afterwards, the breast cancer cells were incubated with increasing concentrations of SnO2 NPs, and inhibition of cell proliferation was assessed by the viability assay. Furthermore, the quantification of reactive oxygen species (ROS) and apoptosis were examined by flow cytometry followed by superoxide dismutase (SOD) and catalase (CAT) activity as well as mitochondrial membrane potential assays. The expression levels of phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), mechanistic target of rapamycin (mTOR), B-cell lymphoma 2 (Bcl-2), and Bax were also assessed by western blot and quantitative real time PCR (qRT-PCR). It was shown that SnO2 NPs, 30 nm, with potential colloidal stability selectively prevented the proliferation of MCF-7 in comparison with MCF-10A cells and triggered ROS production, apoptosis, deactivation of SOD and CAT activity, and mitigation of mitochondrial membrane potential. Moreover, SnO2 NPs stimulated mitochondrial-mediated apoptosis pathway by overexpression of Bax/Bcl-2 and downregulation of p-PI3K/p-AKT/p-mTOR signaling pathway. This data elucidates the possible mechanisms by which SnO2 NPs may stimulate their anticancer effects.