PMID- 26519656 OWN - NLM STAT- MEDLINE DCOM- 20170104 LR - 20220331 IS - 1527-3792 (Electronic) IS - 0022-5347 (Linking) VI - 195 IP - 4 Pt 1 DP - 2016 Apr TI - Inhibition of High Basal Level of Autophagy Induces Apoptosis in Human Bladder Cancer Cells. PG - 1126-35 LID - S0022-5347(15)05148-4 [pii] LID - 10.1016/j.juro.2015.10.128 [doi] AB - PURPOSE: Cancer cells adapt to stress by activation of the autophagy pathway primed for survival. A high basal level of autophagic activity was found in human bladder cancer cell lines. We studied the significance of the phenomenon on cancer cell survival. MATERIALS AND METHODS: The immortalized human bladder epithelial cell line SV-HUC-1 and the human bladder cancer cell lines RT-4 and 5637 together with human bladder cancer specimens collected from patients were used. A commercially available bladder cancer microarray was applied to confirm the findings. LC3 (light chain-3) II protein detection was done to determine the presence of autophagy. Caspase 3 and DNA fragmentation was performed to detect apoptosis. RESULTS: Bladder cancer cell lines showed activated autophagic flux compared to SV-HUC-1 cells, prostate cancer cells and breast cancer cells. Results were confirmed in human bladder cancer specimens. Autophagy inhibition by Baf (bafilomycin) A1, or by knockdown of ATG (autophagy related protein) 7 or 12 induced cytotoxicity in multiple human bladder cell lines. Induction of apoptosis was found in cells with autophagy inhibition. Although the disruption of mitochondria membrane potential or the generation of reactive oxygen species was detected in Baf A1 treated cells, intensity was mild and not thought to be related to apoptosis of bladder cancer cells. CONCLUSIONS: Our results indicate that autophagy is required for the growth and survival of human bladder cancer cells. CI - Copyright (c) 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved. FAU - Lin, Yi-Chia AU - Lin YC AD - Division of Urology, Department of Surgery, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, Republic of China; School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan, Republic of China. FAU - Lin, Ji-Fan AU - Lin JF AD - Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, Republic of China. FAU - Wen, Sheng-I AU - Wen SI AD - Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, Republic of China. FAU - Yang, Shan-Che AU - Yang SC AD - Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, Republic of China. FAU - Tsai, Te-Fu AU - Tsai TF AD - Division of Urology, Department of Surgery, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, Republic of China; School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan, Republic of China. FAU - Chen, Hung-En AU - Chen HE AD - Division of Urology, Department of Surgery, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, Republic of China. FAU - Chou, Kuang-Yu AU - Chou KY AD - Division of Urology, Department of Surgery, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, Republic of China; School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan, Republic of China. FAU - Hwang, Thomas I-Sheng AU - Hwang TI AD - Division of Urology, Department of Surgery, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, Republic of China; Department of Urology, Taipei Medical University, Taipei, Taiwan, Republic of China; School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan, Republic of China. Electronic address: thomashwang0820@gmail.com. LA - eng PT - Journal Article DEP - 20151028 PL - United States TA - J Urol JT - The Journal of urology JID - 0376374 RN - 0 (Macrolides) RN - 88899-55-2 (bafilomycin A1) SB - IM MH - Aged MH - Aged, 80 and over MH - Apoptosis/*drug effects MH - Autophagy/*drug effects MH - Female MH - Humans MH - Macrolides/*pharmacology MH - Male MH - Middle Aged MH - Tumor Cells, Cultured MH - Urinary Bladder Neoplasms/*pathology OTO - NOTNLM OT - apoptosis OT - autophagy OT - bafilomycin A1 OT - cell survival OT - urinary bladder neoplasms EDAT- 2015/11/01 06:00 MHDA- 2017/01/05 06:00 CRDT- 2015/11/01 06:00 PHST- 2015/10/16 00:00 [accepted] PHST- 2015/11/01 06:00 [entrez] PHST- 2015/11/01 06:00 [pubmed] PHST- 2017/01/05 06:00 [medline] AID - S0022-5347(15)05148-4 [pii] AID - 10.1016/j.juro.2015.10.128 [doi] PST - ppublish SO - J Urol. 2016 Apr;195(4 Pt 1):1126-35. doi: 10.1016/j.juro.2015.10.128. Epub 2015 Oct 28.