Fluoxetine regulates cell growth inhibition of interferon-α

Lin,Yu-Min; Yu,Bu-Chin; Chiu,Wen-Tai; Sun,Hung-Yu; Chien,Yu-Chieh; Su,Hui-Chen; Yen,Shu-Yang; Lai,Hsin-Wen; Bai,Chyi-Huey; Young,Kung-Chia; Tsao,Chiung-Wen

doi:10.3892/ijo.2016.3650

Fluoxetine regulates cell growth inhibition of interferon-α

Authors:
- Yu-Min Lin
- Bu-Chin Yu
- Wen-Tai Chiu
- Hung-Yu Sun
- Yu-Chieh Chien
- Hui-Chen Su
- Shu-Yang Yen
- Hsin-Wen Lai
- Chyi-Huey Bai
- Kung-Chia Young
- Chiung-Wen Tsao
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Affiliations: Department of Gastroenterology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, R.O.C., Departments of Animal Resource Sciences and Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan, Department of Biomedical Engineering, College of Engineering, National Cheng Kung University, Tainan, Taiwan, R.O.C., Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, R.O.C., Department of Pharmacy, Chi-Mei Medical Center, Tainan, Taiwan, R.O.C., Department of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan, Taiwan, R.O.C., Department of Public Health, College of Medicine, Taipei Medical University, Taipei, Taiwan, R.O.C., Department of Nursing, Chung Hwa University of Medical Technology, Tainan County, Taiwan, R.O.C.
Published online on: August 5, 2016 https://doi.org/10.3892/ijo.2016.3650
Pages: 1746-1754

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Abstract

Fluoxetine, a well-known anti-depression agent, may act as a chemosensitizer to assist and promote cancer therapy. However, how fluoxetine regulates cellular signaling to enhance cellular responses against tumor cell growth remains unclear. In the present study, addition of fluoxetine promoted growth inhibition of interferon-alpha (IFN-α) in human bladder carcinoma cells but not in normal uroepithelial cells through lessening the IFN-α-induced apoptosis but switching to cause G1 arrest, and maintaining the IFN-α-mediated reduction in G2/M phase. Activations and signal transducer and transactivator (STAT)-1 and peroxisome proliferator-activated receptor alpha (PPAR-α) were involved in this process. Chemical inhibitions of STAT-1 or PPAR-α partially rescued bladder carcinoma cells from IFN-α-mediated growth inhibition via blockades of G1 arrest, cyclin D1 reduction, p53 downregulation and p27 upregulation in the presence of fluoxetine. However, the functions of both proteins were not involved in the control of fluoxetine over apoptosis and maintained the declined G2/M phase of IFN-α. These results indicated that activation of PPAR-α and STAT-1 participated, at least in part, in growth inhibition of IFN-α in the presence of fluoxetine.

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