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para ‐Phenylenediamine induces apoptosis through activation of reactive oxygen species‐mediated mitochondrial pathway, and inhibition of the NF‐κB , m TOR , and W nt pathways in human urothelial cells
Author(s) -
Reena Kasi,
Ng Khuen Yen,
Koh Rhun Yian,
Gnanajothy Ponnudurai,
Chye Soi Moi
Publication year - 2017
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.22233
Subject(s) - apoptosis , reactive oxygen species , wnt signaling pathway , viability assay , microbiology and biotechnology , annexin , programmed cell death , chemistry , western blot , pi3k/akt/mtor pathway , biology , signal transduction , biochemistry , gene
ABSTRACT para ‐Phenylenediamine (PPD) has long been used in two‐thirds of permanent oxidative hair dye formulations. Epidemiological studies and in vivo studies have shown that hair dye is a suspected carcinogen of bladder cancer. However, the toxicity effects of PPD to human bladder remains elusive. In this study, the effects of PPD and its involvement in the apoptosis pathways in human urothelial cells (UROtsa) was investigated. It was demonstrated that PPD decreased cell viability and increased the number of sub‐G 1 hypodiploid cells in UROtsa cells. Cell death due to apoptosis was detected using Annexin V binding assay. Further analysis showed PPD generated reactive oxygen species (ROS), induced mitochondrial dysfunction through the loss of mitochondrial membrane potential and increased caspase‐3 level in UROtsa cells. Western blot analysis of PPD‐treated UROtsa cells showed down‐regulation of phosphorylated proteins from NF‐κB, mTOR, and Wnt pathways. In conclusion, PPD induced apoptosis via activation of ROS‐mediated mitochondrial pathway, and possibly through inhibition of NF‐κB, mTOR, and Wnt pathways. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 265–277, 2017.