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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.
AuthorsArun George Paul, Bala Chandran, Neelam Sharma-Walia
JournalTranslational research : the journal of laboratory and clinical medicine (Transl Res) Vol. 161 Issue 6 Pg. 447-68 (Jun 2013) ISSN: 1878-1810 [Electronic] United States
PMID23523954 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2013 Mosby, Inc. All rights reserved.
Chemical References
  • Anti-Inflammatory Agents, Non-Steroidal
  • Antineoplastic Agents
  • Cyclooxygenase Inhibitors
  • Pyrazoles
  • Receptors, Eicosanoid
  • Sulfonamides
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Celecoxib
Topics
  • Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
  • Antineoplastic Agents (pharmacology)
  • Apoptosis (drug effects)
  • Celecoxib
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival (drug effects)
  • Cyclooxygenase 2 (metabolism)
  • Cyclooxygenase Inhibitors (pharmacology)
  • Drug Screening Assays, Antitumor
  • Drug Synergism
  • Herpesviridae Infections (drug therapy, metabolism, virology)
  • Herpesvirus 4, Human (pathogenicity)
  • Herpesvirus 8, Human (pathogenicity)
  • Humans
  • Lymphoma, B-Cell (metabolism, pathology, virology)
  • Molecular Targeted Therapy (methods)
  • Pyrazoles (pharmacology)
  • Receptors, Eicosanoid (antagonists & inhibitors, metabolism)
  • Sulfonamides (pharmacology)

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