Abstract 2155: Novel combinations of nano-formulated ferulic acid and aspirin show high potential for chemoprevention of pancreatic cancer

Abstract

Abstract Pancreatic cancer ranks as the fourth most deadly form of cancer in the United States with about 37,000 deaths each year. This study evaluated the chemopreventive potential of combinations of free and nano-encapsulated mixtures of ferulic acid (FA) and aspirin (ASP) in low doses to human pancreatic cancer cells, MIA PaCa-2 and Panc-1. Cell lines were tested according to published protocols wherein cells were seeded in 96-well microplates and incubated with the unmodified and modified combinations for 72 h and analyzed using MTS cell viability assay method. Apoptosis was measured by flow cytometry. Results demonstrated that free FA (200 µM) and ASP (1 mM) combinations on average reduced cell viability by 60% (P<0.001), and also induced cell apoptosis by 47% (P<0.001) on the two cell lines. However, when individual agents (FA 200 μM; ASP 1mM) were tested, they were virtually ineffective in reducing cell viability, thus indicating an additive/synergistic effect of the two agents in combination. Subsequently, nano-formulations of FA and ASP (nano-FA and nano-ASP) were prepared by encapsulating the agents within solid lipid nanoparticles (SLNs) and tested on the same cell lines. Prior to this, nano-FA and nano-ASP were evaluated for particle sizes and encapsulation efficiencies. Initial particle sizes were 183± 46 nm (nano-FA) and 229±67 nm (nano-ASP), respectively. Furthermore, the encapsulation efficiencies were high for both nano-FA (86%) and nano-ASP (78%). The combination mixture of nano-FA (25 µM) and nano-ASP (25 µM) reduced the cell viability of MIA PaCa-2 and Panc-1 cells by 70% (P<0.001), and also induced cell apoptosis by 30% (P<0.01), thus reducing the dosage of FA by 8-fold and that of ASP by 40-fold to elicit a comparable response as the mixture of the free FA and ASP. Finally, a trans-AM NF-κB transcription factor assay kit was used to help understand the mechanism. Our results demonstrate that nano-FA and nano-ASP combinations significantly down-regulated NF-κB DNA binding activity in MIA PaCa-2 and Panc-1 cells. In conclusion, convincing evidence is provided of the chemopreventive potential of combinations of FA and ASP against pancreatic cancer, especially when formulated within a nanotechnology-based delivery system. Citation Format: Arvind Thakkar, Jeffrey Wang, Sunil Prabhu. Novel combinations of nano-formulated ferulic acid and aspirin show high potential for chemoprevention of pancreatic cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2155. doi:10.1158/1538-7445.AM2014-2155