title: Inhibition of High Basal Level of Autophagy Induces Apoptosis in Human Bladder Cancer Cells.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: 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.
authors.forename: Yi-Chia
authors.initials: YC
authors.lastname: Lin
authors.affiliation: Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, Republic of China.
authors.forename: Ji-Fan
authors.initials: JF
authors.lastname: Lin
authors.affiliation: Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, Republic of China.
authors.forename: Sheng-I
authors.initials: SI
authors.lastname: Wen
authors.affiliation: Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, Republic of China.
authors.forename: Shan-Che
authors.initials: SC
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Te-Fu
authors.initials: TF
authors.lastname: Tsai
authors.affiliation: Division of Urology, Department of Surgery, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, Republic of China.
authors.forename: Hung-En
authors.initials: HE
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Kuang-Yu
authors.initials: KY
authors.lastname: Chou
authors.affiliation: 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.
authors.forename: Thomas I-Sheng
authors.initials: TI
authors.lastname: Hwang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D005260:Female; D006801:Humans; D018942:Macrolides / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000473:pathology*
chemical_list: D018942:Macrolides; C040929:bafilomycin A1
keywords: apoptosis; autophagy; bafilomycin A1; cell survival; urinary bladder neoplasms