Peer-reviewed veterinary case report
Perphenazine drug shows anti-tumor effects on canine lymphoma cells
By Tsuji, Shunya et al.·Published in The Journal of veterinary medical science·2016·Joint Faculty of Veterinary Medicine, Japan·View original on PubMed →
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Original publication title: Anti-tumor effects of perphenazine on canine lymphoma.
- Species:
- dog
Plain-English summary
A study found that perphenazine, a medication typically used for mental health conditions, may help treat lymphoma in dogs. In tests with canine T-cell lymphoma cells, perphenazine was shown to reduce cell survival and trigger cell death. This effect was linked to changes in specific proteins that help regulate cell growth and death. The results suggest that perphenazine could be a potential treatment option for dogs with lymphoma, but further research is needed to confirm its effectiveness in actual patients.
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Abstract
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 tumor suppressor. Perphenazine (PPZ) is one of the phenothiazines and widely used as an antipsychotic drug. Recently, it is reported that PPZ directly binds with scaffolding subunit of PP2A complex and exerts anti-tumor effects on human T cell acute lymphoblastic leukemia. However, the effect of PPZ on canine lymphoma has not been studied. Here, we investigated the potential therapeutic role of PPZ and its molecular mechanism in canine T-cell lymphoma. In canine T-cell lymphoma cell lines, UL-1 and Ema, PPZ decreased cell survival in a dose-dependent manner. Increased caspase 3 activity and Annexin V positive cells 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 the first time revealed that PPZ induced canine lymphoma cells apoptosis through Akt dephosphorylation via PP2A activation. Our study suggests the possible therapeutic application of phenothiazines for canine T-cell lymphoma.
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Search related cases →Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/27150024/