Yi-Chia Lin1, Ji-Fan Lin2, Sheng-I Wen2, Shan-Che Yang2, Te-Fu Tsai1, Hung-En Chen3, Kuang-Yu Chou1, Thomas I-Sheng Hwang4. 1. 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. 2. Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, Republic of China. 3. Division of Urology, Department of Surgery, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, Republic of China. 4. 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.
Abstract
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.
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 humanbladder 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 humanbladder 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 humanbladder 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 humanbladder cancer cells.
Authors: Sergey A Dyshlovoy; Ramin Madanchi; Jessica Hauschild; Katharina Otte; Winfried H Alsdorf; Udo Schumacher; Vladimir I Kalinin; Alexandra S Silchenko; Sergey A Avilov; Friedemann Honecker; Valentin A Stonik; Carsten Bokemeyer; Gunhild von Amsberg Journal: BMC Cancer Date: 2017-02-01 Impact factor: 4.430
Authors: Diego Martin-Sanchez; Miguel Fontecha-Barriuso; Maria Dolores Sanchez-Niño; Adrian M Ramos; Ramiro Cabello; Carmen Gonzalez-Enguita; Andreas Linkermann; Ana Belén Sanz; Alberto Ortiz Journal: Cell Death Dis Date: 2018-01-25 Impact factor: 8.469