Fig. 3

(1) AgNPs upregulates caspase-8 which leads to stimulate and activate pro-apoptotic proteins- Bid, tBid, and further increase the release of cytochrome C from mitochondria which activates Apaf-1, then forms Apoptosome. Following the formation of Apoptosome, caspases are activated and result in apoptosis. AgNPs also directly upregulates cleaved caspase-3 to increase the process of apoptosis. (2) AgNPs results in mitochondrial apoptosis by increasing the permeability of the mitochondrial membrane and reducing the production of ATP. AgNPs also upregulates the apoptotic protein- Bak and Bax, which increase the release of cytochrome C and induce apoptosis. (3) AgNPs acts on genetic material DNA and causes damages by the increasing generation of ROS that causes oxidative stress and damages the DNA. These nanoparticles inhibit the protein kinases (PKC) and cause cell cycle arrest at the G2/M phase. AgNPs upregulates P-23 Protein which is responsible to activate the apoptosis process by activating other pro-apoptotic protein. Following the DNA damage intracellular pro-apoptotic proteins are released to activate caspases and cause cell death. (4) Vascular endothelial growth factor (VEGF), which is the pro-angiogenic factor involved in the activation of signaling pathways that promotes cell proliferation and migration through tyrosine kinase receptor (VEGFR2) and cause angiogenesis in tumor cells. This mechanism is inhibited by AgNPs by suppressing VEGF induced cell proliferation