Abstract LB-049: Differential effects of functionalized and non-functionalized short multi-wall carbon nanotubes on survival of pancreatic cancer cells

Abstract

Abstract Pancreatic cancer is an aggressive type of cancer with poor prognosis and low five-year survival rate. Current treatments such as chemotherapy and radiation therapy are not effective. Thus, new therapeutic strategies are urgently needed to treat patients with this devastating disease and to improve their prognosis. Carbon nanotubes (CNTs) constitute a novel nanomaterial extensively studied to develop and exploit their potential in biomedical applications (e.g. drug delivery vehicles and diagnostic agents), including cancer nanobiomedicine. Modification of CNTs with functional groups may improve their aqueous solubility and selectively facilitate the attachment of drugs as well as macromolecules to CNTs, thereby creating new avenues for designing novel and highly targeted drugs. Even though the putative cytotoxicity of functionalized and non-functionalized CNTs is poorly understood, it can be gainfully exploited to enhance the efficacy of anti-cancer drugs. The aim is this study is to investigate the hypothesis that functionalized and non-functionalized CNTs exert differential cytotoxic effects on pancreatic cancer cells. We employed the MTT assay to determine the effects of functionalized and non-functionalized short multi-wall carbon nanotubes (SMWCNTs) on survival of PANC1 cells and Western-blot analysis to elucidate some of the cell survival/proliferation mechanisms (e.g., ERG) underlying the effects induced by SMWCNTs. We used the Seahorse XFp technology to examine the effects of the SMWCNTs on cellular energetics (especially glycolysis & mitochondrial metabolism) in pancreatic cancer cells. Additionally, we employed Annexin V/PI staining in combination with flow cytometry to determine the effects of SMWCNTs in inducing apoptosis in MiaPaca-2 cells. Dose-response studies on pancreatic cancer cells using the MTT assay indicated non-functionalized CNTs to be more cytotoxic than functionalized CNTs. Cell signaling studies indicate no alteration in AKT & phospho-AKT levels between functionalized & non-functionalized CNTs treatment. However, phospho-ERK levels were observed to consistently decrease with increasing concentrations of non-functionalized CNTs. Flow cytometric analysis showed increased apoptotic cell death with non-functionalized CNTs relative to that with functionalized CNTs. Overall, results from these studies indicate the differential effects of CNTs (functionalized versus non-functionalized) on pancreatic cancer cells and as such they may have implications in designing novel therapies for treatment of pancreatic cancer. Citation Format: Alok Bhushan, Rutika Kokate, Vilas Desai, Annie Chhun, Gagan Kaushal, Yao Zhang, James Lai. Differential effects of functionalized and non-functionalized short multi-wall carbon nanotubes on survival of pancreatic cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-049.