A Potential Therapeutic Application of SET/I2PP2A Inhibitor OP449 for Canine T-cell Lymphoma

Journal of Veterinary Medical Science

Ryotaro YABE²  Takuya MIZUNO³  Hideyoshi KAWASAKI²  Koichi SATO²  Michael P. VITEK⁴  Takashi OHAMA²  Dale J. CHRISTENSEN¹  Nobuyuki FUJIWARA² 

[1] Department of Medicine (Hematology), Duke University, Durham, NC, U.S.A.;Laboratory of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Japan;Laboratory of Veterinary Internal Medicine, Joint Faculty of Veterinary Medicine, Yamaguchi University, Japan;Departments of Medicine (Neurology) and Neurobiology, Duke University, Durham, NC, U.S.A.

关键词: apoptosis;    canine lymphoma;    OP449;    protein phosphatase 2A;    SET;   

DOI  :  10.1292/jvms.12-0366

学科分类：兽医学

来源: Japanese Society of Veterinary Science

【 摘 要 】

References(31)Cited-By(8)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.

【 授权许可】

Unknown