Induction of Apoptosis by Tungsten Carbide‐Cobalt Nanoparticles in JB6 Cells Involves ROS Generation through both ‘Extrinsic’ and ‘Intrinsic’ Apoptotic Pathways

Abstract

Tungsten Carbide‐Cobalt (WC‐Co) nanoparticle composites have wide applications because of their hardness and toughness. In this study, apoptosis and related signaling induced by WC‐Co were investigated. Electron spin resonance (ESR) and fluorescent staining indicated that both WC‐Co nano‐ and fine particles stimulated reactive oxygen species (ROS) generation. Catalase inhibit WC‐Co‐induced ROS as well as mitochondrial membrane permeability damage, indicating that H2O2 may play an important role in the cytotoxicity induced by WC‐Co. Further studies indicated that WC‐Co nanoparticles elicited a higher cytotoxicity and apoptotic induction than fine particles. Western‐blot analysis showed an activation of proapoptotic factors including Fas, FADD, caspase 3, 8 and 9, BID, and BAX. Lamin A and beta‐actin were cleaved. Interestingly, WC‐Co particles also induced Bcl‐2, an anti‐apoptotic factor, up‐regulation. In addition, both cytochrome c and AIF were up‐regulated and released from mitochondria to the cytoplasm. The results demonstrate that apoptosis induced by WC‐Co involve both ‘extrinsic’ and ‘intrinsic’ apoptotic pathways and nanoparticles exhibit higher cytotoxicity and apoptotic induction than fine particles.