Abstract
In spite of chemotherapeutic and surgical advances, pancreatic cancer continues to have a dismal prognosis. Metastasis due to tumor cell migration remains the most critical challenge in treating pancreatic cancer, and conventional chemotherapy is rarely curative. In the quest for more novel molecules to fight this disease, we tested the hypothesis that the Pseudomonas aeruginosa quorum sensing signal molecule N-3-oxo-dodecanoyl-L-homoserine lactone (O-DDHSL) would be cytotoxic to and reduce mobility of pancreatic carcinoma cells (Panc-1 and Aspc-1). Results showed a decrease in cell viability from apoptosis, diminished colony formation, and inhibition of migration of the evaluated pancreatic carcinoma cell lines. Also, cell viability decreased in the presence of O-DDHSL when cells were grown in matrigel basement membrane matrix. While messenger RNA for IQGAP-1 decreased in Panc-1 and HPDE cells upon exposure to O-DDHSL, no change was observed in Aspc-1 cells. Cofilin mRNA expression was found to be increased in both HPDE and Panc-1 cells with marginal decrease in Aspc-1 cells. RhoC, a Rho-family GTPase involved in cell motility, increased in the presence of O-DDHSL, suggesting a possible compensatory response to alteration in other migration associated genes. Our results indicate that O-DDHSL could be an effective biomolecule in eukaryotic systems with multimodal function for essential molecular targeting in pancreatic cancer.
Highlights
Pancreatic cancer is the fourth leading cause of cancer related mortality in the United States
We explored the possibility that human pancreatic tumor cells could respond to Quorum sensing (QS) molecules of P. aeruginosa bacteria, anticipating that such signaling molecules could modulate the growth and migration characteristics as well as gene expression of the cells
We observed that the long acyl chain QS molecule ODDHSL was effective in modulating the pancreatic carcinoma cell properties, while O-HSSL with a short chain acyl group was not as effective
Summary
Pancreatic cancer is the fourth leading cause of cancer related mortality in the United States. According to 2013 statistics from the American Cancer Society, approximately 45,220 people (22,740 men and 22,480 women) were expected to be diagnosed with pancreatic cancer during that year. Patients are most commonly diagnosed with pancreatic cancer in an advanced stage and the disease is generally refractory to chemotherapy [1]. 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 [3]. These facts indicate that novel compounds are required for treatment to combat this disease
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