NiWo4- RGO composite exerts cytotoxic effects on pancreatic carcinoma cells via a cross-talk between reactive oxygen species-independent canonical autophagy of the mitochondria and epithelial-mesenchymal transition

Abstract

Nanotechnology for its appliance in medicine ranges from several applications such as in biosensors, drug carriers and nanomaterials as drug possibilities or cytotoxic agents without a drug being loaded onto them. Based on this intention, Nickel tungstate- Reduced graphene oxide (NiWO4-RGO) nanocomposites were prepared and characterized by fourier-transform infrared spectroscopy (FTIR), X-Ray diffraction (XRD), Energy dispersive X-ray spectroscopy (EDS), dynamic light scattering (DLS) and transmission electron microscope (TEM). The structural and compositional analyses using FTIR, XRD and EDS indicated that the NiWO4-RGO composite was synthesized. The composites had an optimal mean size of 125.6 nm and polydispersity index (PDI) of 0.156 as per DLS. Further, the cytotoxic effects of the composite on pancreatic ductal adenocarcinoma (PANC-1) cells were determined. The half maximal inhibitory concentration (IC50) value for its toxic effects on PANC-1 cells was 270 ± 8.93 μg/mL. To determine the mechanistic effect, mitochondrial membrane potential (ΔΨm), intracellular ROS and acridine orange/ethidium bromide (AO/EB) staining were studied along with the expression of a set of autophagy and EMT-related genes by using real-time PCR. The outcomes indicate that the mechanism of cytotoxic effects of the composite was related to reactive oxygen species (ROS)-independent canonical autophagy of the mitochondria with a possible influence of ferroptosis and crosstalk with epithelial-mesenchymal transition (EMT). Also, it was found that composites were safe to use on normal cells including L929 mouse fibroblasts and Human Dermal Fibroblasts (HDFs). According to the authors, this is the first-ever international report on determination of the cytotoxic effects of NiWO4-RGO nanocomposite on any in vitro cancer cell type and elucidation of the subsequent mechanisms along with its biocompatibility on normal cells.