PMID- 25034786
OWN - NLM
STAT- MEDLINE
DCOM- 20151102
LR  - 20211203
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 4
DP  - 2014 Jul 18
TI  - Clioquinol induces pro-death autophagy in leukemia and myeloma cells by 
      disrupting the mTOR signaling pathway.
PG  - 5749
LID - 10.1038/srep05749 [doi]
LID - 5749
AB  - Clioquinol is an anti-microbial drug, and it was recently found to induce cancer 
      cell death. In the present study, clioquinol was found to trigger autophagy by 
      inducing LC3 lipidation and autophagosome formation which was abolished by an 
      autophagy inhibitor 3-methyladenine. Further study showed clioquinol displayed no 
      effects on PI3KC3 or Beclin 1 expression but downregulated the expression and the 
      enzymatic activity of mammalian target of Rapamycin (mTOR), a critical modulator 
      of autophagy. Moreover, clioquinol inhibited the catalytic activity of the mTOR 
      complex 1, thus suppressing phosphorylation of P70S6K and 4E-BP1, two major 
      proteins associated with autophagy in the mTORC1 signaling pathway. Clioquinol 
      induced leukemia and myeloma cell apoptosis, however, addition of autophagy 
      inhibitor 3-methyladenine attenuated this kind of cell death. Therefore, this 
      study demonstrated that clioquinol induces autophagy in associated with apoptosis 
      in leukemia and myeloma cells by disrupting mTOR signaling pathway.
FAU - Cao, Biyin
AU  - Cao B
AD  - 1] Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-psycho- 
      diseases, Department of Pharmacology, College of Pharmaceutical Sciences, Soochow 
      University, Suzhou, 215123, China [2] Cyrus Tang Hematology Center, Soochow 
      University, Suzhou, 215123, China [3].
FAU - Li, Jie
AU  - Li J
AD  - 1] Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-psycho- 
      diseases, Department of Pharmacology, College of Pharmaceutical Sciences, Soochow 
      University, Suzhou, 215123, China [2] Cyrus Tang Hematology Center, Soochow 
      University, Suzhou, 215123, China [3].
FAU - Zhou, Xiumin
AU  - Zhou X
AD  - Department of Oncology, The First Affiliated Hospital of Soochow University, 
      Suzhou, 215106, China.
FAU - Juan, Jiaxiang
AU  - Juan J
AD  - Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-psycho- 
      diseases, Department of Pharmacology, College of Pharmaceutical Sciences, Soochow 
      University, Suzhou, 215123, China.
FAU - Han, Kunkun
AU  - Han K
AD  - 1] Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-psycho- 
      diseases, Department of Pharmacology, College of Pharmaceutical Sciences, Soochow 
      University, Suzhou, 215123, China [2] Cyrus Tang Hematology Center, Soochow 
      University, Suzhou, 215123, China.
FAU - Zhang, Zubin
AU  - Zhang Z
AD  - 1] Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-psycho- 
      diseases, Department of Pharmacology, College of Pharmaceutical Sciences, Soochow 
      University, Suzhou, 215123, China [2] Cyrus Tang Hematology Center, Soochow 
      University, Suzhou, 215123, China.
FAU - Kong, Yan
AU  - Kong Y
AD  - Department of Neurology, The First Affiliated Hospital of Soochow University, 
      Suzhou, 215106, China.
FAU - Wang, Jianrong
AU  - Wang J
AD  - Cyrus Tang Hematology Center, Soochow University, Suzhou, 215123, China.
FAU - Mao, Xinliang
AU  - Mao X
AD  - 1] Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-psycho- 
      diseases, Department of Pharmacology, College of Pharmaceutical Sciences, Soochow 
      University, Suzhou, 215123, China [2] Cyrus Tang Hematology Center, Soochow 
      University, Suzhou, 215123, China [3] Collaborative Innovation Center of 
      Hematology, Soochow University, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140718
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (BECN1 protein, human)
RN  - 0 (Beclin-1)
RN  - 0 (Membrane Proteins)
RN  - 0 (Multiprotein Complexes)
RN  - 7BHQ856EJ5 (Clioquinol)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.137 (Class Ib Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis Regulatory Proteins/metabolism
MH  - Autophagy/*drug effects
MH  - Beclin-1
MH  - Cell Line, Tumor
MH  - Class Ib Phosphatidylinositol 3-Kinase/metabolism
MH  - Clioquinol/*pharmacology
MH  - Drug Screening Assays, Antitumor
MH  - Humans
MH  - Leukemia/drug therapy/pathology
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Membrane Proteins/metabolism
MH  - Multiple Myeloma/drug therapy/pathology
MH  - Multiprotein Complexes/metabolism
MH  - Phosphorylation
MH  - Protein Processing, Post-Translational
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases/*metabolism
PMC - PMC4102920
EDAT- 2014/07/19 06:00
MHDA- 2015/11/03 06:00
PMCR- 2014/07/18
CRDT- 2014/07/19 06:00
PHST- 2014/03/14 00:00 [received]
PHST- 2014/07/02 00:00 [accepted]
PHST- 2014/07/19 06:00 [entrez]
PHST- 2014/07/19 06:00 [pubmed]
PHST- 2015/11/03 06:00 [medline]
PHST- 2014/07/18 00:00 [pmc-release]
AID - srep05749 [pii]
AID - 10.1038/srep05749 [doi]
PST - epublish
SO  - Sci Rep. 2014 Jul 18;4:5749. doi: 10.1038/srep05749.