Te-Fu Tsai,1,2 Po-Chun Chen,3,4 Yi-Chia Lin,1,2 Kuang-Yu Chou,1,2 Hung-En Chen,1 Chao-Yen Ho,1,5 Ji-Fan Lin,3 Thomas I-Sheng Hwang1,2,6 1Division of Urology, Department of Surgery, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; 2Division of Urology, School of Medicine, Fu-Jen Catholic University, New Taipei, Taiwan; 3Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; 4Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan;

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... te of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 6Department of Urology, Taipei Medical University, Taipei, TaiwanCorrespondence: Thomas I-Sheng HwangDivision of Urology, Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 11102, TaiwanTel +886-2-28332211 Ext 2065Fax +886-2-28389404Email thomashwang0828@gmail.comPo-Chun Chen Email blibra1002@gmail.comPurpose: Nuclear factor (erythroid-derived 2)-like 2, also known as NFE2L2 or NRF2, a transcription factor capable of upregulating antioxidant response element (ARE)-mediated expression and cytoprotective proteins, plays critical roles in chemoprevention, inflammation and aging. NRF2 has recently been proposed as a novel target for cancer chemoprevention. The fungicide miconazole has shown promising antiproliferative effects in cancer cells.Materials and Methods: After miconazole treatment, the p62-KEAP1-NRF2 activation was analyzed by qPCR and Western blot. The nuclear translocation indicating NRF2 activation was further confirmed by immunofluorescence. Finally, the ROS production was detected by CM-H2DCFDA staining.Results: We demonstrate in this study that miconazole dramatically increases NRF2 activation in bladder cancer cells, in a dose- and time-dependent manner. Interestingly, levels of expression of p62, a noncanonical pathway that mediates NRF2 activation, appeared to increase in accordance with NRF2. We also investigated levels of the negative regulator kelch-like ECH-associated protein 1 (KEAP1), which i [...]