Abstract 4785: Silver nanoparticles induce apoptosis in squamous lung cancer cell by regulation of cyclic AMP response element-binding protein: regulating its upstream oxidative stress-dependent Ras signaling pathways

Abstract

Abstract Recently, much effort has been devoted to the development of biomedical applications (drug delivery system and as therapeutic drugs themselves) 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 cytotoxicity in cancer cells. 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 and it might be by regulation of oxidative stress in tumorigenesis. In H520 cell, human lung squamous cancer cell line, reactive oxygen species (ROS) were increased. In western blot analysis, Ras signaling molecule in which ROS is involved was constitutively overexpressed and the levels of pErk, pRsk, pAkt and pCREB were increased in H520 cell. Incubation of the H520 cells with silver NPs (at dose of 100 or 200 μM) substantially suppressed the ROS in H520 cell and Ras-Erk-Rsk-CREB and Ras-PI3K-Akt signaling pathway in a dose-dependent manner. We subsequently demonstrated that silver NPs inhibited the caspase-dependent pathway, determined by increased levels of PARP (poly (ADP-ribose) polymerase) cleavage. In this study, we suggest that silver NPs induce apoptosis in human lung cancer cells by attenuation of oxidative stress in lung cancer cell line and ROS-dependent Ras signaling which involves CREB signaling pathways and may be useful as a therapeutic strategy for cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4785. doi:10.1158/1538-7445.AM2011-4785