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Inhibition of High Basal Level of Autophagy Induces Apoptosis in Human Bladder Cancer Cells.

By: Yi-Chia Lin, Ji-Fan Lin, Sheng-I Wen, Shan-Che Yang, Te-Fu Tsai, Hung-En Chen, Kuang-Yu Chou, Thomas I-Sheng Hwang

Division of Urology, Department of Surgery, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.
2015-10-16; doi: 10.1016/j.juro.2015.10.128

Abstract

Purpose

Cancer cells adapt to the stress by activation of the autophagy pathway primed for survival. High basal level of autophagic activity was found in human bladder cancer cell lines. We conduct a study to show the significance on cancer cell survival on the phenomenon.

Materials

A immortalized human bladder epithelial cells (SV-HUC-1) and human bladder cancer cell lines (RT-4 and 5637) together with human bladder cancer specimen collected from patients were used. A commercially available bladder cancer microarray was employed to confirm the findings. LC-3 II protein detection was used to determine the presence of autophagy. Caspase 3 and DNA fragmentation was used to detect apoptosis.

Results

Bladder cancer cell lines exhibited activated autophagic flux comparing to SV-HUC-1 cells, prostate cancer cells and breast cancer cells. The results were confirmed in human bladder cancer specimens. Autophagy inhibition by Baf A1 or knockdown of ATG7 or ATG12 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 were detected in Baf A1-treated cells, the intensity was mild and not thought to be related to the apoptosis of the bladder cancer cells.

Conclusions

Our results indicated that autophagy is required for growth and survival of human bladder cancer cells.