title: Potent reactive oxygen species-JNK-p38 activation by sodium salicylate potentiates death of primary effusion lymphoma cells.
abstract: BACKGROUND
  Primary effusion lymphoma (PEL) is a rare but aggressive form of non-Hodgkin's B-cell lymphoma in immunodeficient patients. Resistance to conventional chemotherapeutic regimens is common in PEL and contributes to a very poor prognosis; hence, novel potent anti-PEL agents are required. Anticancer effects of non-steroidal anti-inflammatory drugs (NSAIDs) are well-established in epithelial cancer but are unclear in hematological malignancies. Therefore, the anticancer activities of selected NSAIDs, sodium salicylate (NaS), on PEL cell lines are of interest.
  
  
  METHODS
  Anti-proliferation of NaS on PEL cell lines was shown by MTT. Apoptosis induction and caspase activations were determined by flow cytometry analysis. ROS production was accessed by DCFH-DA. Western blot was performed to determine molecular mechanisms.
  
  
  RESULTS
  NaS effectively inhibited cell proliferation of all PEL cell lines. Caspase-dependent apoptosis was demonstrated and simultaneous induction of reactive oxygen species production and c-Jun N-terminal kinases (JNK)-p38 activation was observed prior to apoptosis induction, and these might be responsible for NaS-induced apoptosis.
  
  
  CONCLUSIONS
  Significant anticancer effects of NaS on PEL cell lines were found. A novel role of NaS for PEL treatment is suggested.
authors.affiliation: Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto, 860-0811, Japan. okadas@kumamoto-u.ac.jp.
authors.forename: Kulthida
authors.initials: K
authors.lastname: Vaeteewoottacharn
authors.forename: Manthana
authors.initials: M
authors.lastname: Mitchai
authors.forename: Pattaravadee
authors.initials: P
authors.lastname: Srikoon
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Hattori
authors.forename: Ryusho
authors.initials: R
authors.lastname: Kariya
authors.forename: Kouki
authors.initials: K
authors.lastname: Matsuda
authors.forename: Sopit
authors.initials: S
authors.lastname: Wongkham
authors.forename: Seiji
authors.initials: S
authors.lastname: Okada
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D054685:Lymphoma, Primary Effusion / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012980:Sodium Salicylate / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases; D012980:Sodium Salicylate
keywords: Primary effusion lymphoma; apoptosis; reactive oxygen species; sodium salicylate