title: Concurrent targeting of eicosanoid receptor 1/eicosanoid receptor 4 receptors and COX-2 induces synergistic apoptosis in Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus associated non-Hodgkin lymphoma cell lines.
abstract: The effective antitumorigenic potential of nonsteroidal anti-inflammatory drugs (NSAIDs) and eicosonoid (EP; EP1-4) receptor antagonists prompted us to test their efficacy in Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) related lymphomas. Our study demonstrated that (1) EP1-4 receptor protein levels vary among the various non-Hodgkin's lymphoma (NHL) cell lines tested (BCBL-1:KSHV+/EBV-;BC-3: KSHV+/EBV-; Akata/EBV+: KSHV-/EBV+; and JSC-1 cells: KSHV+/EBV + cells); (2) 5.0 μM of EP1 antagonist (SC-51322) had a significant antiproliferative effect on BCBL-1, BC-3, Akata/EBV+, and JSC-1 cells; (3) 50.0 μM of EP2 antagonist (AH6809) was required to induce a significant antiproliferative effect on BCBL-1, Akata/EBV+, and JSC-1 cells; (4) 5.0 μM of EP4 antagonist (GW 627368X) had a significant antiproliferative effect on BC-3, Akata/EBV+, and JSC-1 cells; (5) COX-2 selective inhibitor celecoxib (5.0 μM) had significant antiproliferative effects on BCBL-1, BC-3, Akata/EBV+, and JSC-1 cells; and (6) a combination of 1.0 μM each of celecoxib, SC-51322 and GW 627368X could potentiate the proapoptotic properties of celecoxib or vice-versa. Overall, our studies identified the synergistic antiproliferative effect of NSAIDs and EP receptor blockers on KSHV and EBV related B cell malignancies.
authors.affiliation: H. M. Bligh Cancer Research Laboratories, Department of Microbiology and Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.
authors.forename: Arun George
authors.initials: AG
authors.lastname: Paul
authors.forename: Bala
authors.initials: B
authors.lastname: Chandran
authors.forename: Neelam
authors.initials: N
authors.lastname: Sharma-Walia
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000068579:Celecoxib; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006566:Herpesviridae Infections / Q000188:drug therapy / Q000378:metabolism / Q000821:virology; D004854:Herpesvirus 4, Human / Q000472:pathogenicity; D019288:Herpesvirus 8, Human / Q000472:pathogenicity; D006801:Humans; D016393:Lymphoma, B-Cell / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D058990:Molecular Targeted Therapy / Q000379:methods*; D011720:Pyrazoles / Q000494:pharmacology; D018055:Receptors, Eicosanoid / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D018055:Receptors, Eicosanoid; D013449:Sulfonamides; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000068579:Celecoxib