Open Access

Perphenazine exerts antitumor effects on HUT78 cells through Akt dephosphorylation by protein phosphatase 2A

  • Authors:
    • Shunya Tsuji
    • Naoki Kohyanagi
    • Takuya Mizuno
    • Takashi Ohama
    • Koichi Sato
  • View Affiliations

  • Published online on: December 15, 2020     https://doi.org/10.3892/ol.2020.12374
  • Article Number: 113
  • Copyright: © Tsuji et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.
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February-2021
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Spandidos Publications style
Tsuji S, Kohyanagi N, Mizuno T, Ohama T and Sato K: Perphenazine exerts antitumor effects on HUT78 cells through Akt dephosphorylation by protein phosphatase 2A. Oncol Lett 21: 113, 2021
APA
Tsuji, S., Kohyanagi, N., Mizuno, T., Ohama, T., & Sato, K. (2021). Perphenazine exerts antitumor effects on HUT78 cells through Akt dephosphorylation by protein phosphatase 2A. Oncology Letters, 21, 113. https://doi.org/10.3892/ol.2020.12374
MLA
Tsuji, S., Kohyanagi, N., Mizuno, T., Ohama, T., Sato, K."Perphenazine exerts antitumor effects on HUT78 cells through Akt dephosphorylation by protein phosphatase 2A". Oncology Letters 21.2 (2021): 113.
Chicago
Tsuji, S., Kohyanagi, N., Mizuno, T., Ohama, T., Sato, K."Perphenazine exerts antitumor effects on HUT78 cells through Akt dephosphorylation by protein phosphatase 2A". Oncology Letters 21, no. 2 (2021): 113. https://doi.org/10.3892/ol.2020.12374