Potent reactive oxygen species-JNK-p38 activation by sodium salicylate potentiates death of primary effusion lymphoma cells

Anticancer Res. 2014 Apr;34(4):1865-71.

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.

Materials and 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.

Conclusion: Significant anticancer effects of NaS on PEL cell lines were found. A novel role of NaS for PEL treatment is suggested.

Keywords: Primary effusion lymphoma; apoptosis; reactive oxygen species; sodium salicylate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Lymphoma, Primary Effusion / metabolism*
  • Reactive Oxygen Species / metabolism*
  • Sodium Salicylate / pharmacology*
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Antineoplastic Agents
  • Reactive Oxygen Species
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Caspases
  • Sodium Salicylate