Royal Jelly–Mediated Silver Nanoparticles Show Promising Anticancer Effect on HeLa and A549 Cells Through Modulation of the VEGFa/PI3K/Akt/MMP‐2 Pathway

Abstract

ABSTRACTIn recent years, nanotechnology has revolutionized various sectors, particularly in nanomedicine, where nanomaterials are used for diagnosis, monitoring, control, prevention, and treatment. Among these, silver nanoparticles (AgNPs) stand out due to their remarkable antimicrobial and cytotoxic properties. Traditional chemical synthesis of AgNPs poses significant environmental and health risks. This study introduces a novel, eco‐friendly synthesis method using royal jelly (RJ), a nutrient‐rich secretion from honeybees, to produce AgNPs with potent anticancer effects. Our research provides a detailed investigation into RJ‐mediated AgNPs’ modulation of the VEGFa/PI3K/Akt/MMP‐2 pathway in HeLa and A549 cancer cell lines. AgNP characterization was performed by applying UV–Vis spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM) in combination with selected area electron diffraction (SAED). Cell signaling system components were determined by ELISA analysis. The cells were subjected to staining with hematoxylin and eosin to visualize the treatment’s effects. This study focuses on the green synthesis of AgNPs using RJ and its bioactivity against cancer cells. It provides a detailed characterization of the nanoparticles and examines their effects on cancer cells, specifically HeLa cervical cancer and A549 lung cancer cell lines. Green synthesized AgNPs demonstrate significant cytotoxic effects against HeLa and A549 cancer cell lines. The underlying molecular mechanisms contributing to their anticancer activity were elucidated. Our findings revealed a significant decrease in arginase activity upon exposure to AgNPs, accompanied by reductions in PI3K and phosphorylated and total Akt levels, indicative of pathway inhibition. Additionally, RJAgNP demonstrated a capacity to reduce nitric oxide levels and suppress angiogenesis‐related factors like VEGF and MMP‐2 and inflammation‐related factors like TNF‐α and COX‐2, thus impeding angiogenesis and metastasis. Moreover, our results shed light on the involvement of reactive oxygen intermediates (ROIs) in mediating apoptotic pathways, as evidenced by the increase in malondialdehyde (MDA) concentration and the corresponding decrease in Akt levels, ultimately promoting death in cancer cells. Our study contributes significantly to the field of nanomedicine and cancer therapy by introducing the use of green synthesis AgNPs using RJ and providing in‐depth insights into their molecular mechanisms of anticancer action. Our research findings demonstrate the anticancer potential of RJ‐AgNPs by targeting the VEGFa/PI3K/Akt/MMP‐2 pathway and modulation of ROS/RNS in cancer cells.