Antipsychotic agent pimozide promotes reversible proliferative suppression by inducing cellular quiescence in liver cancer

Chen,Jia‑Jie; Zhang,Li‑Na; Cai,Nan; Zhang,Zhen; Ji,Kunmei

doi:10.3892/or.2019.7229

Antipsychotic agent pimozide promotes reversible proliferative suppression by inducing cellular quiescence in liver cancer

Authors:
- Jia‑Jie Chen
- Li‑Na Zhang
- Nan Cai
- Zhen Zhang
- Kunmei Ji
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Affiliations: Department of Biochemistry and Molecular Biology, School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, P.R. China, College of Life Science and Oceanography, Shenzhen University, Shenzhen, Guangdong 518060, P.R. China
Published online on: July 11, 2019 https://doi.org/10.3892/or.2019.7229
Pages: 1101-1109
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The antipsychotic drug pimozide has been found to exhibit anticancer effects. Previously, it was demonstrated that pimozide inhibits hepatocellular carcinoma (HCC) cell growth, but its pharmacodynamic characteristics remain unclear. The aim of the present study was to investigate the reversibility and mechanism of the ability of pimozide to inhibit cell proliferation in liver cancer. Cell viability was determined by Cell Counting Kit‑8 and colony formation assay. The cell cycle distribution was analyzed by flow cytometry with Ki‑67 and PI staining. ROS production of HCC cells was detected with DCFH‑DA and inhibited with NAC treatment. Western blot assay was performed to detect the expression of related signaling molecules in HCC cells. Our results showed that pimozide promoted G0/G1 phase arrest in HCC cell lines without significant cell death. Its anti‑proliferative effects on HCC cells were reversible, consistent with involvement of cell quiescence and reactive oxygen species (ROS) production. Pimozide enhanced inhibition of HCC cell proliferation by sorafenib. In conclusion, elucidation of pimozide's reversible proliferation inhibition in liver cancer and additive activity with a well‑established anticancer drug warrants further exploration of the potential of pimozide as an adjuvant anticancer therapy.

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