Abstract 4464: Effect of bacterial quorum sensing lactones on human pancreatic carcinoma cells

Abstract

Abstract INTRODUCTION Pancreatic cancer (PC) is the fourth leading cause of cancer related mortality in the United States. In spite of the discovery of gemcitabine, administered either alone or in combination with other drugs, the survival rate of 5% has remained unchanged for several decades now. In this study, we hypothesize that bacterial quorum sensing molecules such as N-3-oxo-dodecanoyl-L-homoserine lactone (O-DDHSL) could affect pancreatic carcinoma cell phenotype and characteristics. Elucidation of the mechanism of action of O-DDHSL could lead to the development of more effective analogs and novel therapeutic targets in PC. MATERIALS AND METHODS Human pancreatic carcinoma cells (Panc-1 and Aspc-1) was grown in DMEM-F12 media with 10% FBS at 37oC. Normal pancreatic ductal epithelial cells (HPDE) were maintained in keratinocyte serum free media. Total RNA was extracted from the cells and converted to cDNA which served as a template for qRT-PCR amplification in the presence of various gene primers. The effect of O-DDHSL on pancreatic carcinoma cell phenotype, apoptosis, viability, migration, proliferation and colony forming ability was investigated. RESULTS Both Panc-1 and Aspc-1 cell viability decreased in a concentration dependent manner in the presence of O-DDHSL (IC50 = 120 ± 5 μM; P ≤ 0.02) and (IC50 = 48 ± 8 μM; P ≤ 0.02), respectively. O-DDHSL had only minimal effect on HPDE cell viability. Apoptosis and inhibition of cell migration in Panc-1 and Aspc-1 cells was observed in the presence of O-DDHSL. Variable effect on migration associated genes such as IQGAP-1, cofilin and rhoC was noted in these cells upon O-DDHSL treatment as determined by qRT-PCR as well as protein expression by Western analysis. CONCLUSIONS In conclusion, the combined findings from our study demonstrate that O-DDHSL decreases pancreatic carcinoma cell viability, promotes apoptosis by activating caspases, and inhibits cell migration. O-DDHSL also modulates genes responsible for migration such as RhoC, cofilin and IQGAP-1 in these cells. Citation Format: Senthil R. Kumar, Jeffrey Bryan. Effect of bacterial quorum sensing lactones on human pancreatic carcinoma cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4464. doi:10.1158/1538-7445.AM2015-4464