PMID- 28978086
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 8
IP  - 40
DP  - 2017 Sep 15
TI  - AMPK activation-dependent autophagy compromises oleanolic acid-induced 
      cytotoxicity in human bladder cancer cells.
PG  - 67942-67954
LID - 10.18632/oncotarget.18980 [doi]
AB  - Autophagy is an evolutionarily conserved catabolic process in eukaryotic cells, 
      which allows cells to overcome a wide array of of stresses and has recently been 
      shown to result in drug resistance. This study examined the effect of autophagy 
      on oleanolic acid (OA)-induced cytotoxicity against bladder cancer cells. Our 
      study demonstrated that OA inhibited cell viability, proliferation, and induced 
      apoptosis in bladder cancer lines T24 and EJ. Furthermore, OA induced autophagy 
      in both cell lines by activating AMP-activated protein kinase (AMPK), inhibiting 
      mechanistic target of rapamycin (mTOR) and promoting unc-51 like autophagy 
      activating kinase 1 (ULK1). Moreover, inhibiting autophagy by siRNA to autophagy 
      related 7 (ATG7) or with autophagy inhibitor bafilomycin A1 and 3-methyladenine 
      (3-MA) or AMPK inhibitor dorsomorphin (compound C) promoted OA-induced deaths of 
      bladder cancer cells. In contrast, either autophagy activator rapamycin or AMPK 
      activator acadesine (AICAR) compromised OA-induced anti-cancer effect. Our 
      findings suggested that OA induced protective autophagy through AMPK-mTOR-ULK1 
      signaling pathway in bladder cancer cells and OA in combination with autophagy 
      inhibitor might be a novel alternative for the treatment of bladder cancer.
FAU - Song, Yarong
AU  - Song Y
AD  - Department of Urology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430022, China.
FAU - Zhang, Peng
AU  - Zhang P
AD  - Department of Urology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430022, China.
FAU - Sun, Yadong
AU  - Sun Y
AD  - Department of Urology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430022, China.
FAU - Li, Xuechao
AU  - Li X
AD  - Department of Urology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430022, China.
FAU - Chen, Lifeng
AU  - Chen L
AD  - Department of Urology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430022, China.
FAU - Xiao, Yajun
AU  - Xiao Y
AD  - Department of Urology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430022, China.
FAU - Xing, Yifei
AU  - Xing Y
AD  - Department of Urology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430022, China.
LA  - eng
PT  - Journal Article
DEP - 20170704
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC5620226
OTO - NOTNLM
OT  - AMPK
OT  - autophagy
OT  - bladder cancer
OT  - cytotoxicity
OT  - oleanolic acid
COIS- CONFLICTS OF INTEREST The authors declare no conflicts of interest.
EDAT- 2017/10/06 06:00
MHDA- 2017/10/06 06:01
PMCR- 2017/09/15
CRDT- 2017/10/06 06:00
PHST- 2016/10/22 00:00 [received]
PHST- 2017/06/16 00:00 [accepted]
PHST- 2017/10/06 06:00 [entrez]
PHST- 2017/10/06 06:00 [pubmed]
PHST- 2017/10/06 06:01 [medline]
PHST- 2017/09/15 00:00 [pmc-release]
AID - 18980 [pii]
AID - 10.18632/oncotarget.18980 [doi]
PST - epublish
SO  - Oncotarget. 2017 Jul 4;8(40):67942-67954. doi: 10.18632/oncotarget.18980. 
      eCollection 2017 Sep 15.