Trifluoperazine and Its Analog Suppressed the Tumorigenicity of Non-Small Cell Lung Cancer Cell; Applicability of Antipsychotic Drugs to Lung Cancer Treatment
Joo Yeon Jeong,
Haangik Park,
Hong Yoo,
Eun-Jin Kim,
Borami Jeon,
Jong Deog Lee,
Dawon Kang,
Changjoon Justin Lee,
Sun Ha Paek,
Eun Joo Roh,
Gwan-Su Yi,
Sang Soo Kang
Affiliations
Joo Yeon Jeong
Department of Anatomy & Convergence Medical Science, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Korea
Haangik Park
Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea
Hong Yoo
Division of Pulmonology and Allergy, Department of Internal Medicine, Gyeongsang National University Hospital, College of Medicine, Gyeongsang National University, Jinju 52727, Korea
Eun-Jin Kim
Department of Physiology & Convergence Medical Science, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Korea
Borami Jeon
Chemical Kinomics Research Center, Korea Institute of Science and Technology, Seoul 02792, Korea
Jong Deog Lee
Division of Pulmonology and Allergy, Department of Internal Medicine, Gyeongsang National University Hospital, College of Medicine, Gyeongsang National University, Jinju 52727, Korea
Dawon Kang
Department of Physiology & Convergence Medical Science, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Korea
Changjoon Justin Lee
Center for Glia-Neuron Interaction and Neuroscience, Korea Institute of Science and Technology, Seoul 02792, Korea
Sun Ha Paek
Department of Neurosurgery, College of Medicine, Seoul National University, Seoul 03080, Korea
Eun Joo Roh
Chemical Kinomics Research Center, Korea Institute of Science and Technology, Seoul 02792, Korea
Gwan-Su Yi
Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea
Sang Soo Kang
Department of Anatomy & Convergence Medical Science, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Korea
Despite significant advances in diagnostic and therapeutic technologies, lung cancer remains the leading cause of cancer-related mortality worldwide. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases. Recently, some antipsychotics have been shown to possess anticancer activity. However, the effects of antipsychotics on NSCLC need to be further explored. We examined the effects of trifluoperazine (TFP), a commonly used antipsychotic drug, and its synthetic analogs on A549 human lung cancer cells. In addition, cell proliferation analysis, colony formation assay, flow cytometry, western blot analysis, and in vivo xenograft experiments were performed. Key genes and mechanisms possibly affected by TFP are significantly related to better survival outcomes in lung cancer patients. Treatment with TFP and a selected TFP analog 3dc significantly inhibited the proliferation, anchorage-dependent/independent colony formation, and migration of A549 cells. Treatment with 3dc affected the expression of genes related to the apoptosis and survival of A549 cells. Treatment with 3dc promoted apoptosis and DNA fragmentation. In all experiments, including in vivo studies of metastatic lung cancer development, 3dc had more substantial anticancer effects than TFP. According to our analysis of publicly available clinical data and in vitro and in vivo experiments, we suggest that some kinds of antipsychotics prevent the progression of NSCLC. Furthermore, this study indicates a synthetic TFP analog that could be a potential therapeutic for lung cancer.
