Glucose-capped fisetin silver nanoparticles induced cytotoxicity and ferroptosis in breast cancer cells: A molecular perspective

Abstract

Breast cancer is a prevalent malignancy that poses a significant health threat globally among the women population. In this study, we sought to investigate the cytotoxic and apoptotic effects of glucose-capped fisetin silver nanoparticles (GF-Ag NPs) against the MDA-MB-231 breast cancer cell line. GF-Ag NPs were synthesized and characterized using UV–Vis spectroscopy, X-ray diffractometer, Transmission electron microscopy, Dynamic light scattering, and Photoluminescence. The UV–Vis spectroscopy showed a surface plasmon resonance peak at 432 nm corresponds to Ag. The X-ray diffractometer revealed face-centric cubic nanocrystallites indicating the reduction of Ag+ ions by glucose. Transmission electron microscopy revealed that the glucose-capped fisetin silver nanoparticles had a spherical structure with an average particle size of ∼55 ± 2 nm. The elemental composition analysis with Energy Dispersive X-Ray Analysis indicates 47.04 % of carbon, 3.48 % of oxygen, and 49.48 % of silver. The FT-IR spectra of GF-AG NPs when compared to spectra of fisetin, glucose, and fisetin Ag NPs revealed distinct peak shifts. Diving deeper into cell-based studies, we observed distinct morphological alterations in cells treated with glucose-capped fisetin silver nanoparticles, which included cell shrinkage, detachment, membrane blebbing, and distorted shape. Moreover, the MTT assay demonstrated a significant reduction in cell viability with an IC50 (half-maximal inhibitory concentration) of 11.275 ± 0.197 μg/mL. MDA-MB-231 cells treated with glucose-capped fisetin silver nanoparticles showed signs of apoptosis, decreased mitochondrial membrane potential, and elevated Reactive oxygen species (ROS) production. Gene expression profiling was performed using reverse transcriptase polymerase chain reaction (RT-PCR). The gene expression analysis revealed an upregulation of SLC7A11, SLC40A1, NRF2F, NOX2, and NOX5 genes that are associated with various crucial cellular events. Our study highlights the potential of glucose-capped fisetin silver nanoparticles as a therapeutic agent for breast cancer treatment.