The PPARγ agonist Troglitazone induces autophagy, apoptosis and necroptosis in bladder cancer cells.
Bladder cancer is a major public health problem worldwide, with relatively high morbidity. However, there are few studies on drug development for bladder cancer. Troglitazone (TZ) is a synthetic ligand of peroxisome proliferator-activated receptor-γ, and it can induce apoptosis and autophagy in a variety of cancer cells. Several studies have indicated that TZ affects both cell growth and differentiation progress and has an inhibitory effect on urinary cancer cells. However, this drug's effect on bladder cancer cells remains largely unknown. Here, we report that TZ induced autophagy and enhanced apoptosis in T24 cells. Autophagic blockage resulted in the attenuation of TZ-dependent apoptosis. Necrostatin-1, an inhibitor of necroptosis, was found to reduce light chain 3 (LC3)-II accumulation and partially rescue the loss of cell viability induced by TZ. It was demonstrated that TZ activated autophagy concurrent with the activation of the adenosine monophosphate-dependent protein kinase (AMPK) signaling pathway. AMPK inhibition led to a reduction in LC3-II levels, which were responsive to TZ treatment. Overall, TZ induced multiple types of programmed cell death in bladder cancer cells, and while the autophagy induced by the agonist contributed to the apoptotic process, crosstalk or switching between the different types of cell death likely occurred.
1] State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China [2] College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
S
S
Yan
Department of Urology, Peking University First Hospital, Institute of Urology, Peking University, Beijing, China.
X
X
Yang
1] State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China [2] School of Life Science, Liaoning University, Shenyang, China.
T
T
Chen
Department of Urology, Peking University First Hospital, Institute of Urology, Peking University, Beijing, China.
Z
Z
Xi
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
X
X
Jiang
D000263:Adenylate Kinase / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002839:Chromans / Q000494:pharmacology*; D006801:Humans; D009336:Necrosis; D047495:PPAR gamma / Q000819:agonists*; D015398:Signal Transduction; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone; D001749:Urinary Bladder Neoplasms / Q000473:pathology*
D002839:Chromans; D047495:PPAR gamma; D045162:Thiazolidinediones; D000263:Adenylate Kinase; D000077288:Troglitazone