A potential therapeutic application of SET/I2PP2A inhibitor OP449 for canine T-cell lymphoma.

Published

Journal Article

Lymphoma is one of the most common malignant tumors in canine. Chemotherapy results in a high rate of remission; however, relapse and clinical drug resistance are usually seen within a year. Protein phosphatase 2A (PP2A) acts as a tumor suppressor and plays a critical role in mammalian cell transformation. Increased protein levels of SET, endogenous PP2A inhibitor, have been reported to correlate with poor prognosis in human leukemia. Here, we test the potential therapeutic role for a SET antagonist in canine lymphoma. We observed SET protein levels increased in multiple canine lymphoma cell lines compared with primary peripheral blood cells. A novel SET antagonist OP449 increased PP2A activity and effectively killed SET high-expressing canine lymphoma cells, but not SET low-expressing cells. Caspase-3 activation and enhanced Annexin V positive staining were observed after OP449 treatment, suggesting apoptotic cell death by OP449. Consistent with this, pan-caspase inhibitor Z-VAD-FMK blocked OP449 induced cell death. These data demonstrated the potential therapeutic application of SET antagonists for canine lymphoma.

Full Text

Duke Authors

Cited Authors

  • Fujiwara, N; Kawasaki, H; Yabe, R; Christensen, DJ; Vitek, MP; Mizuno, T; Sato, K; Ohama, T

Published Date

  • January 2013

Published In

Volume / Issue

  • 75 / 3

Start / End Page

  • 349 - 354

PubMed ID

  • 23131782

Pubmed Central ID

  • 23131782

Electronic International Standard Serial Number (EISSN)

  • 1347-7439

International Standard Serial Number (ISSN)

  • 0916-7250

Digital Object Identifier (DOI)

  • 10.1292/jvms.12-0366

Language

  • eng