Perphenazine exerts antitumor effects on HUT78 cells through Akt dephosphorylation by protein phosphatase 2A
- Shunya Tsuji
- Naoki Kohyanagi
- Takuya Mizuno
- Takashi Ohama
- Koichi Sato
Affiliations: Laboratory of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi 753‑8515, Japan, The Laboratory of Molecular Diagnostics and Therapeutics, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi 753‑8515, Japan
- Published online on: December 15, 2020 https://doi.org/10.3892/ol.2020.12374
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Sezary syndrome is a rare type of non‑Hodgkin lymphoma. Protein phosphatase 2A (PP2A) is an important tumor suppressor whose activity is widely inhibited in a variety of tumors. Recently, reactivation of PP2A has attracted increasing attention as a promising approach for cancer therapy. Phenothiazine anti‑psychotic perphenazine (PPZ) exerts antitumor effects by reactivating PP2A. The present study investigated the molecular mechanism underling the antitumor effects of PPZ in the neuroblastoma rat sarcoma oncogene (NRAS)‑mutated Sezary syndrome cell line, HUT78. The results of the present study demonstrated that PPZ induced the dephosphorylation of Akt and ERK1/2, and triggered apoptosis in HUT78 cells. In addition, a PP2A inhibitor blocked the PPZ‑mediated dephosphorylation of Akt but did not affect that of ERK1/2. The pharmacological inhibition of Akt and ERK1/2 signaling revealed that Akt activity serves an important role in the survival of HUT78 cells. The present data suggested that suppressing Akt activity by PP2A activation may be an attractive antitumor strategy for NRAS‑mutated Sezary syndrome.