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Title: Quinacrine induces the apoptosis of human leukemia U937 cells through FOXP3/miR-183/β-TrCP/SP1 axis-mediated BAX upregulation

Abstract

Quinacrine, which is clinically used as an antimalarial drug, has anti-cancer activity. However, mechanism underlying its cytotoxic effect remains to be completely elucidated. In the present study, we investigated the cytotoxic effect of quinacrine on human leukemia U937 cells. Quinacrine-induced apoptosis of U937 cells was accompanied with ROS generation, mitochondrial depolarization, and BAX upregulation. Quinacrine-treated U937 cells showed ROS-mediated p38 MAPK activation and ERK inactivation, which in turn upregulated FOXP3 transcription. FOXP3-mediated miR-183 expression decreased β-TrCP mRNA stability and suppressed β-TrCP-mediated SP1 degradation, thus increasing SP1 expression in U937 cells. Upregulated SP1 expression further increased BAX expression. BAX knock-down attenuated quinacrine-induced mitochondrial depolarization and increased the viability of quinacrine-treated cells. Together, our data indicate that quinacrine-induced apoptosis of U937 cells is mediated by mitochondrial alterations triggered by FOXP3/miR-183/β-TrCP/SP1 axis-mediated BAX upregulation. - Highlights: • Quinacrine induces U937 cell apoptosis via upregulation of BAX. • Quinacrine induces FOXP3 expression via p38 MAPK activation and ERK inactivation. • FOXP3-mediated miR-183 expression reduces β-TrCP mRNA stability. • Suppression of β-TrCP-mediated SP1 degradation increases BAX expression. • Quinacrine elicits FOXP3/miR-183/β-TrCP/SP1 axis-mediated BAX upregulation.

Authors:
;  [1];  [2]; ;  [1];  [1];  [3]
  1. Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan (China)
  2. Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China)
  3. (China)
Publication Date:
OSTI Identifier:
22722944
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 334; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; LEUKEMIA; MITOCHONDRIA; PHOSPHORUS 38

Citation Formats

Huang, Chia-Hui, Lee, Yuan-Chin, Chen, Ying-Jung, Wang, Liang-Jun, Shi, Yi-Jun, Chang, Long-Sen, and Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan. Quinacrine induces the apoptosis of human leukemia U937 cells through FOXP3/miR-183/β-TrCP/SP1 axis-mediated BAX upregulation. United States: N. p., 2017. Web. doi:10.1016/J.TAAP.2017.08.019.
Huang, Chia-Hui, Lee, Yuan-Chin, Chen, Ying-Jung, Wang, Liang-Jun, Shi, Yi-Jun, Chang, Long-Sen, & Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan. Quinacrine induces the apoptosis of human leukemia U937 cells through FOXP3/miR-183/β-TrCP/SP1 axis-mediated BAX upregulation. United States. doi:10.1016/J.TAAP.2017.08.019.
Huang, Chia-Hui, Lee, Yuan-Chin, Chen, Ying-Jung, Wang, Liang-Jun, Shi, Yi-Jun, Chang, Long-Sen, and Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan. Wed . "Quinacrine induces the apoptosis of human leukemia U937 cells through FOXP3/miR-183/β-TrCP/SP1 axis-mediated BAX upregulation". United States. doi:10.1016/J.TAAP.2017.08.019.
@article{osti_22722944,
title = {Quinacrine induces the apoptosis of human leukemia U937 cells through FOXP3/miR-183/β-TrCP/SP1 axis-mediated BAX upregulation},
author = {Huang, Chia-Hui and Lee, Yuan-Chin and Chen, Ying-Jung and Wang, Liang-Jun and Shi, Yi-Jun and Chang, Long-Sen and Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan},
abstractNote = {Quinacrine, which is clinically used as an antimalarial drug, has anti-cancer activity. However, mechanism underlying its cytotoxic effect remains to be completely elucidated. In the present study, we investigated the cytotoxic effect of quinacrine on human leukemia U937 cells. Quinacrine-induced apoptosis of U937 cells was accompanied with ROS generation, mitochondrial depolarization, and BAX upregulation. Quinacrine-treated U937 cells showed ROS-mediated p38 MAPK activation and ERK inactivation, which in turn upregulated FOXP3 transcription. FOXP3-mediated miR-183 expression decreased β-TrCP mRNA stability and suppressed β-TrCP-mediated SP1 degradation, thus increasing SP1 expression in U937 cells. Upregulated SP1 expression further increased BAX expression. BAX knock-down attenuated quinacrine-induced mitochondrial depolarization and increased the viability of quinacrine-treated cells. Together, our data indicate that quinacrine-induced apoptosis of U937 cells is mediated by mitochondrial alterations triggered by FOXP3/miR-183/β-TrCP/SP1 axis-mediated BAX upregulation. - Highlights: • Quinacrine induces U937 cell apoptosis via upregulation of BAX. • Quinacrine induces FOXP3 expression via p38 MAPK activation and ERK inactivation. • FOXP3-mediated miR-183 expression reduces β-TrCP mRNA stability. • Suppression of β-TrCP-mediated SP1 degradation increases BAX expression. • Quinacrine elicits FOXP3/miR-183/β-TrCP/SP1 axis-mediated BAX upregulation.},
doi = {10.1016/J.TAAP.2017.08.019},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = ,
volume = 334,
place = {United States},
year = {2017},
month = {11}
}