Biosynthesized Protein-Capped Silver Nanoparticles Induce ROS-Dependent Proapoptotic Signals and Prosurvival Autophagy in Cancer Cells

Abstract

In recent years, the use of silver nanoparticles (AgNPs) in biomedical applications has shown an unprecedented boost along with simultaneous expansion of rapid, high-yielding, and sustainable AgNP synthesis methods that can deliver particles with well-defined characteristics. The present study demonstrates the potential of metal-tolerant soil fungal isolate Penicillium shearii AJP05 for the synthesis of protein-capped AgNPs. The particles were characterized using standard techniques, namely, UV–visible spectroscopy, transmission electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. The anticancer activity of the biosynthesized AgNPs was analyzed in two different cell types with varied origin, for example, epithelial (hepatoma) and mesenchymal (osteosarcoma). The biological NPs (bAgNPs) with fungal-derived outer protein coat were found to be more cytotoxic than bare bAgNPs or chemically synthesized AgNPs (cAgNPs). Elucidation of the molecular mechanism revealed that bAgNPs induce cytotoxicity through elevation of reactive oxygen species (ROS) levels and induction of apoptosis. Upregulation of autophagy and activation of JNK signaling were found to act as a prosurvival strategy upon bAgNP treatment, whereas ERK signaling served as a prodeath signal. Interestingly, inhibition of autophagy increased the production of ROS, resulting in enhanced cell death. Finally, bAgNPs were also found to sensitize cells with acquired resistance to cisplatin, providing valuable insights into the therapeutic potential of bAgNPs. To the best of our knowledge, this is the first study that provides a holistic idea about the molecular mechanisms behind the cytotoxic activity of protein-capped AgNPs synthesized using a metal-tolerant soil fungus.

Autophagy Regulated by Gain of Function Mutant p53 Enhances Proteasomal Inhibitor-Mediated Cell Death through Induction of ROS and ERK in Lung Cancer Cells

“…Previous reports show that mitogen activated protein kinase (MAPK) signaling pathways are able to modulate autophagy and determine cell fate [39]. There are also a growing number of reports stating that, in certain conditions, the MAPK-ERK can promote cell death [40, 41]. Interestingly, an increase in phospho-ERK indicative of its activation was observed in cells treated with ALLN, which went down with autophagy inhibition by CQ (Figure 6(a)).…”

Biosynthesis of silver nanoparticles employing Trichoderma harzianum with enzymatic stimulation for the control of Sclerotinia sclerotiorum

“…Similar results were obtained using the Allium cepa assay to evaluate the effects of low concentrations of silver nanoparticles synthesized using the plant Swertia chirata 62 . The toxic effects caused by silver nanoparticles may be due to the generation of reactive oxygen species and DNA damage, leading to apoptosis, as well as the release of Ag + ions, which depends on the rate of dissolution of the nanoparticles within the cells 63–65 .…”

Nanosafety

“…Nanotechnologies propose a diversity of possible for relevance in different areas of food technology that comprise packaging, processing, quality and shelf life, ingredients and additives. The complexity in characterizing assorted nanomaterials used the food industry and biological systems incomplete information on toxicology and lack optimal test methods the risk appraisal and supervision of nanotechnologies harder [37,38]. A preventive advance with detailed life cycle estimation and strongly required procedures to stakeholders connecting for diverse activities as formulating best practices that will support the growth of nanotechnology in the food sector for regulating the potential risk to humans and the environment.…”