Anti-tumor effects of perphenazine on canine lymphoma

Journal of Veterinary Medical Science

Ryotaro YABE¹  Takuya MIZUNO²  Tatsuya USUI³  Koichi SATO¹  Takashi OHAMA¹  Shunya TSUJI¹ 

[1] Laboratory of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, Yamaguchi University, 1677�?1 Yoshida, Yamaguchi 753�?8515, Japan;Laboratory of Molecular Diagnostics and Therapeutics, Joint Faculty of Veterinary Medicine, Yamaguchi University, Japan;Laboratory of Veterinary Toxicology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Japan

关键词: canine;    lymphoma;    perphenazine;    PP2A;   

DOI  :  10.1292/jvms.15-0707

学科分类：兽医学

来源: Japanese Society of Veterinary Science

【 摘 要 】

References(26)Supplementary materials(1)Lymphoma is one of the most common malignant tumors in canine. Protein phosphatase 2A(PP2A), a well-conserved serine/threonine phosphatase, plays a critical role as a tumorsuppressor. Perphenazine (PPZ) is one of the phenothiazines and widely used as anantipsychotic drug. Recently, it is reported that PPZ directly binds with scaffoldingsubunit of PP2A complex and exerts anti-tumor effects on human T cell acute lymphoblasticleukemia. However, the effect of PPZ on canine lymphoma has not been studied. Here, weinvestigated the potential therapeutic role of PPZ and its molecular mechanism in canineT-cell lymphoma. In canine T-cell lymphoma cell lines, UL-1 and Ema, PPZ decreased cellsurvival in a dose-dependent manner. Increased caspase 3 activity and Annexin V positivecells suggested that PPZ induced apoptosis. PPZ dephosphorylated Akt, MEK1/2 and ERK1/2.Akt inhibitor, but not MEK1/2 inhibitor and ERK1/2 inhibitor, induced cell death,indicating the importance of Akt dephosphorylation for the anti-tumor effect of PPZ.Finally, we observed enhanced PP2A activity by PPZ treatment. The present results for thefirst time revealed that PPZ induced canine lymphoma cells apoptosis through Aktdephosphorylation via PP2A activation. Our study suggests the possible therapeuticapplication of phenothiazines for canine T-cell lymphoma.

【 授权许可】

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