Desipramine induces apoptosis in hepatocellular carcinoma cells

Yang,Dong Kwon; Kim,Shang-Jin

doi:10.3892/or.2017.5723

Desipramine induces apoptosis in hepatocellular carcinoma cells

Authors:
- Dong Kwon Yang
- Shang-Jin Kim
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Affiliations: Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Biosafety Research Institute and Korea Zoonosis Research Institute, Chonbuk National University, Iksan, Jeollabuk-do 54596, Republic of Korea
Published online on: June 15, 2017 https://doi.org/10.3892/or.2017.5723
Pages: 1029-1034

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Abstract

Antitumor effects of antidepressants have been reported in many cancer cell lines. However, anti-proliferative effects of desipramine, a tricyclic antidepressant, in hepatocellular carcinoma are currently unknown. In this study, we examined the effects of desipramine in human hepatoma Hep3B cells. To evaluate anti-proliferative effects of desipramine in Hep3B cells, we determined cell viability, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), mitogen-activated protein kinase (MAPK) activity, and intracellular Ca2+ levels after desipramine treatment. Desipramine reduced cell viability, increased ROS production, and decreased MMP activity in Hep3B cells. In addition, desipramine activated MAPKs (ERK 1/2, JNK, and p38) and increased intracellular Ca2+ levels. Pro-apoptotic effects of desipramine were abolished after MAPK inhibitors (PD98059, SB203580, and SP600125) or N-acetyl-L-cysteine (NAC), as a ROS scavenger, treatments. These findings suggest that desipramine shows anti-proliferative effects in Hep3B cells mediated by promotion of apoptosis, activation of MAPK signaling, and increase in intracellular Ca2+ levels.

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