Biogenic metal nanoformulations induce Bax/Bcl2 and caspase mediated mitochondrial dysfunction in human breast cancer cells (MCF 7)

Abstract

Nanostructures of noble metals have been extensively studied recently because of their impressive physiochemical properties and wide range of applications in biology and medicine. In this study, the anticancer efficacy of green synthesized silver and gold nanoparticles (AgNPs and AuNPs) was assessed against human breast carcinoma cells (MCF-7). Treatment with different concentrations of NPs triggers the cellular toxicity in a dose and time dependent manner. Morphological features of apoptosis were measured using cell wall integrity, acridine orange/ethidium bromide and Hochest staining methods which clearly distinguishes the viable cells and the cells undergoing apoptosis. Flow cytometry and DNA fragmentation analysis were also used to substantiate that NPs induced cytotoxicity was primarily mediated by G2/M cell cycle arrest and apoptosis. NPs provoke intracellular reactive oxygen species that cause damage to various cellular components. Furthermore, the gene expression studies such as reverse transcription – polymerase chain reaction, quantitative polymerase chain reaction and western blot analysis shows the upregulation of Bax, Bcl2, caspases-6 and -9, PARP, p53 and downregulation of Bcl-2 depicts the induction of apoptosis upon exposure to NPs. The overall results clearly shows that green synthesized metal NPs can potentially inhibit the proliferation of MCF-7 cells and trigger apoptosis through Bax/Bcl2 and caspase–cascade mediated mitochondrial dysfunction. This research concludes that biogenic metal nano-drug formulations can be utilized for cancer chemotherapy.