Abstract 4414: Differential effects of functionalized and non-functionalized short multi-wall carbon nanotubes on survival and cell signaling in pancreatic cancer cells.

Abstract

Abstract Pancreatic cancer is an aggressive type of cancer with poor prognosis and low five-year survival rate. Because chemotherapeutic and radiation treatments are not effective, new treatments for this cancer are needed to improve its prognosis. Carbon nanotubes (CNTs) constitute one novel and important nanomaterial extensively examined for potential biomedical applications (e.g., drug delivery vehicles and diagnostic agents). Modification of CNTs with functional groups improves solubility and may serve as attachment site of other molecules and/or drugs. This study elucidated the cytotoxicity induced by CNTs and the underlying mechanisms. We employed MTT assay to determine survival of PANC1 cells treated with different concentrations of short-multi-wall CNTs (SMWCNTs) or SMWCNTs-COOH for 24, 48, and 72 hrs. Our results suggested that functionalization with carboxyl group to SMWCNTs lowers their cytotoxicity. Therefore we hypothesized that the induced cytotoxicity by both SMWCNTs and SMWCNTs-COOH is a result of either up-regulation of apoptotic pathways or down-regulation of cellular survival/proliferation/differentiation pathways or a combination of both. We carried out western-blot analysis to examine the effects of CNTs on ERK, phospho-ERK, AKT, phospho-AKT signal transduction pathways and on the NF-κB pathway. PANC1 cells were treated with 2, 20, and 200 μg/ml SMWCNTs-COOH or SMWCNTs for 48hrs. The expressions of phospho-ERK were decreased in cells treated with 2 μg/ml SMWCNTs-COOH. However, as the concentration of SMWCNTs-COOH increased from 2 to 200 μg/ml, the phospho-ERK expression was increased: however, the total ERK expression was unaffected. The NF-κB expression in the cells was increased compared to control group as the concentration of SMWCNTs-COOH increased from 2 to 200 μg/ml. Our study demonstrates that both SMWCNTs and SMWCNTs-COOH induced cytotoxicity in pancreatic cancer cells and functionalization with carboxyl group lowered their cytotoxicity. One mechanism underlying their cytotoxicity may be the altered regulation of cellular survival/proliferation pathways such as ERK. Thus, our results may have implications in cytotoxicity of SMWCNTs in pancreatic cells and in designing therapies for pancreatic cancer. Citation Format: Yao Zhang, James C.K. Lai, Alok Bhushan, Biomedical and Pharmaceutical Sciences Department,College of Pharmacy, Division of Health Sciences. Differential effects of functionalized and non-functionalized short multi-wall carbon nanotubes on survival and cell signaling in pancreatic cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4414. doi:10.1158/1538-7445.AM2013-4414