Anticancer Activities of Biogenic Silver Nanoparticles Targeting Apoptosis and Inflammatory Pathways in Colon Cancer Cells

Abstract

Colorectal cancer (CRC) progression is a complex process, with an interplay of multiple molecular signaling pathways. Cyclooxygenase-2 (COX-2) and NF-κB are important hallmark proteins responsible for the transition from inflammation to colon cancer. Due to the adverse effects of chemotherapeutic drugs, there is an imperative need to develop new drugs, and recently, nanoparticles found to be promising strategy in tumor detection, prevention and treatment of cancer. Biosynthesis of silver nanoparticles (AgNPs) was achieved with the help of Eucalyptus globulus L. leaf extract. Using a typical XRD pattern, NanoSight and TEM technique, the size and shape of the biogenic AgNPs were determined as ~ 20 nm and spherical. The cytotoxicity study exhibited a dose-dependent effect against HCT116 cells, with an inhibitory concentration (IC50) of 1.152 µg/ml. In addition, AgNPs effectively inhibited the proliferation, colony formation, with increased ROS production compared to untreated cells. Further, mechanistic analysis revealed that AgNPs arrested the cell cycle, downregulated the expression of antiapoptotic, inflammatory, stem cell markers, and upregulated the apoptotic genes in HCT116 cells. In conclusion, for the first time, we report the green synthesis of AgNPs using E. globulus leaf extract that has potential anticancer activity with dual inhibitory action on COX-2 and NF-κB expression.