Oncotarget

Research Papers:

In vitro and in vivo anti-tumor effects of brexpiprazole, a newly-developed serotonin-dopamine activity modulator with an improved safety profile

Shuhei Suzuki, Masahiro Yamamoto _, Keita Togashi, Tomomi Sanomachi, Asuka Sugai, Shizuka Seino, Takashi Yoshioka, Chifumi Kitanaka and Masashi Okada _

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Oncotarget. 2019; 10:3547-3558. https://doi.org/10.18632/oncotarget.26949

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Abstract

Shuhei Suzuki1,2, Masahiro Yamamoto1, Keita Togashi1,3, Tomomi Sanomachi1,2, Asuka Sugai1, Shizuka Seino1, Takashi Yoshioka2, Chifumi Kitanaka1,4 and Masashi Okada1

1 Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata 990-9585, Japan

2 Department of Clinical Oncology, Yamagata University School of Medicine, Yamagata 990-9585, Japan

3 Department of Ophthalmology, Yamagata University School of Medicine, Yamagata 990-9585, Japan

4 Research Institute for Promotion of Medical Sciences, Yamagata University Faculty of Medicine, Yamagata 990-9585, Japan

Correspondence to:

Masahiro Yamamoto,email: masahiro@med.id.yamagata-u.ac.jp
Masashi Okada,email: m-okada@med.id.yamagata-u.ac.jp

Keywords: brexpiprazole; serotonin-dopamine activity modulator; drug repositioning; drug repurposing; survivin

Received: February 25, 2019     Accepted: May 04, 2019     Published: May 28, 2019

ABSTRACT

From the perspective of psycho-oncology, antipsychotics are widely used for patients with cancer. Although some antipsychotic drugs have anti-tumor effects, these antipsychotic drugs are not applicable for cancer patients because of their severe side effects. Brexpiprazole, a novel serotonin-dopamine modulator with an improved side effect profile, was developed as a drug that is structurally and pharmacologically related to aripiprazole, which was reported to have anti-cancer effects. However, it remains unknown whether brexpiprazole has anti-cancer effects. In this study, we examined whether brexpiprazole has anti-tumor effects in cancer cells and cancer stem cells (CSCs) of glioblastoma, pancreatic cancer, and lung cancer. Brexpiprazole suppressed cell growth and induced cell death in the cancer cells and the CSCs, and decreased the CSC properties of the CSCs. Brexpiprazole did not exert any cytotoxic effects on non-cancer cells at the anti-cancer effect-inducing concentration. In the cancer cells and the CSCs, brexpiprazole reduced the expression of survivin, an anti-apoptotic protein, whose reduction sensitizes tumor cells to chemotherapeutic reagents. In the preclinical model in which pancreatic CSCs were subcutaneously implanted into nude mice, brexpiprazole suppressed tumor growth, in addition to reducing the expression of Sox2, a marker for CSCs, and survivin. This suggests that brexpiprazole is a promising antipsychotic drug with anti-tumor effects and an improved safety profile.


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