title: Bacterial quorum sensing molecule N-3-oxo-dodecanoyl-L-homoserine lactone causes direct cytotoxicity and reduced cell motility in human pancreatic carcinoma cells.
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.
authors.affiliation: Comparative Oncology and Epigenetics Laboratory, Veterinary Medicine and Surgery, University of Missouri, Columbia, Missouri, United States of America.
authors.forename: Ashwath S
authors.initials: AS
authors.lastname: Kumar
authors.affiliation: Comparative Oncology and Epigenetics Laboratory, Veterinary Medicine and Surgery, University of Missouri, Columbia, Missouri, United States of America.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Bryan
authors.affiliation: Comparative Oncology and Epigenetics Laboratory, Veterinary Medicine and Surgery, University of Missouri, Columbia, Missouri, United States of America; Harry S. Truman Veterans Hospital, Columbia, Missouri, United States of America.
authors.forename: Senthil R
authors.initials: SR
authors.lastname: Kumar
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D006801:Humans; D010190:Pancreatic Neoplasms; D053038:Quorum Sensing
chemical_list: C088386:homoserine lactone; D015107:4-Butyrolactone