Abstract A18: Silver nanoparticles induce apoptosis by regulation of cyclic AMP response element-binding protein in lung cancer cells

Abstract

Abstract Recently, much effort has been devoted to the development of biomedical applications for nanoparticles (NPs). Silver NPs have been shown various therapeutic effects such as antimicrobial, antioxidant, and anti-inflammatory effects. Recently silver NPs have been shown to induce the apoptotic pathway in vitro. But exact mechanism is not yet established. We conducted this study to determine the mechanisms of silver NPs on cellular apoptosis in non-small cell lung cancer (NSCLC) cell lines using cyclic AMP response element-binding protein (CREB) activity which has been implicated to contribute an important pathobiologic role in lung carcinogenesis and is considered a potential therapeutic target for NSCLC. We hypothesized that constitutively increased CREB and its related signaling pathways can be blocked by silver NPs. To determine cytotoxic effect of silver NPs, several NSCLC cell lines were treated with various concentrations for different times. Among these lung cancer cell lines, H520, human lung squamous carcinoma cell lines, was the most sensitive. FACS analysis also showed that silver NPs induced cell death of H520 cells. Treating H520 cells with silver NPs (100, 200, or 500 M) inhibited CREB activation by blocking the activity of extracellular signal kinase/ribosomal s6 kinase and also by blocking the activity of phosphatidylinositol 3-kinase/Akt. We subsequently confirmed the expression of Bax and Bcl-2 in H520 cells was substantially regulated by silver NPs. We also demonstrated that silver NPs induced the cleavage of apoptosis-related proteins, poly (ADP-ribose) polymerase and caspase-3. In this study, we suggest that silver NPs induce apoptosis in H520 cells by regulation of CREB signaling pathways and may be useful as a therapeutic strategy for cancer. Citation Information: Cancer Prev Res 2010;3(12 Suppl):A18.