PMID- 27689333
OWN - NLM
STAT- MEDLINE
DCOM- 20180226
LR  - 20211204
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 7
IP  - 46
DP  - 2016 Nov 15
TI  - Curcumin targets the TFEB-lysosome pathway for induction of autophagy.
PG  - 75659-75671
LID - 10.18632/oncotarget.12318 [doi]
AB  - Curcumin is a hydrophobic polyphenol derived from the herb Curcumalonga and its 
      wide spectrum of pharmacological activities has been widely studied. It has been 
      reported that Curcumin can induce autophagy through inhibition of the Akt-mTOR 
      pathway. However, the effect of Curcumin on lysosome remains largely elusive. In 
      this study, we first found that Curcumin treatment enhances autophagic flux in 
      both human colon cancer HCT116 cells and mouse embryonic fibroblasts (MEFs). 
      Moreover, Curcumin treatment promotes lysosomal function, evidenced by the 
      increased lysosomal acidification and enzyme activity. Second, Curcumin is 
      capable of suppressing the mammalian target of rapamycin (mTOR). Interestingly, 
      Curcumin fails to inhibit mTOR and to activate lysosomal function in Tsc2-/-MEFs 
      with constitutive activation of mTOR, indicating that Curcumin-mediated lysosomal 
      activation is achieved via suppression of mTOR. Third, Curcumin treatment 
      activates transcription factor EB (TFEB), a key nuclear transcription factor in 
      control of autophagy and lysosome biogenesis and function, based on the following 
      observations: (i) Curcumin directly binds to TFEB, (ii) Curcumin promotes TFEB 
      nuclear translocation; and (iii) Curcumin increases transcriptional activity of 
      TFEB. Finally, inhibition of autophagy and lysosome leads to more cell death in 
      Curcumin-treated HCT116 cells, suggesting that autophagy and lysosomal activation 
      serves as a cell survival mechanism to protect against Curcumin-mediated cell 
      death. Taken together, data from our study provide a novel insight into the 
      regulatory mechanisms of Curcumin on autophagy and lysosome, which may facilitate 
      the development of Curcumin as a potential cancer therapeutic agent.
FAU - Zhang, Jianbin
AU  - Zhang J
AD  - Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, 
      China.
AD  - Department of Physiology, Yong Loo Lin School of Medicine, National University of 
      Singapore, Singapore.
AD  - School of Public Health, Zhejiang University, Institute of Immunology, Zhejiang 
      University, Hangzhou, China.
FAU - Wang, Jigang
AU  - Wang J
AD  - Department of Physiology, Yong Loo Lin School of Medicine, National University of 
      Singapore, Singapore.
FAU - Xu, Jian
AU  - Xu J
AD  - School of Public Health, Zhejiang University, Institute of Immunology, Zhejiang 
      University, Hangzhou, China.
FAU - Lu, Yuanqiang
AU  - Lu Y
AD  - First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 
      China.
FAU - Jiang, Jiukun
AU  - Jiang J
AD  - First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 
      China.
FAU - Wang, Liming
AU  - Wang L
AD  - Department of Physiology, Yong Loo Lin School of Medicine, National University of 
      Singapore, Singapore.
FAU - Shen, Han-Ming
AU  - Shen HM
AD  - Department of Physiology, Yong Loo Lin School of Medicine, National University of 
      Singapore, Singapore.
AD  - NUS Graduate School for Integrative Sciences and Engineering, National University 
      of Singapore, Singapore.
FAU - Xia, Dajing
AU  - Xia D
AD  - School of Public Health, Zhejiang University, Institute of Immunology, Zhejiang 
      University, Hangzhou, China.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Basic Helix-Loop-Helix Leucine Zipper Transcription Factors)
RN  - 0 (TFEB protein, human)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - IT942ZTH98 (Curcumin)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents, Phytogenic/*pharmacology
MH  - Autophagy/*drug effects
MH  - Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics/*metabolism
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Curcumin/*pharmacology
MH  - Fibroblasts
MH  - Gene Knockout Techniques
MH  - HCT116 Cells
MH  - Humans
MH  - Lysosomes/*metabolism
MH  - Mice
MH  - Protein Binding
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/metabolism
MH  - Transcriptional Activation
PMC - PMC5342768
OTO - NOTNLM
OT  - Curcumin
OT  - TFEB
OT  - autophagy
OT  - lysosome
OT  - mTOR
COIS- CONFLICTS OF INTEREST The authors confirm that there are no conflicts of 
      interest.
EDAT- 2016/10/01 06:00
MHDA- 2018/02/27 06:00
PMCR- 2016/11/15
CRDT- 2016/10/01 06:00
PHST- 2016/07/18 00:00 [received]
PHST- 2016/09/16 00:00 [accepted]
PHST- 2016/10/01 06:00 [pubmed]
PHST- 2018/02/27 06:00 [medline]
PHST- 2016/10/01 06:00 [entrez]
PHST- 2016/11/15 00:00 [pmc-release]
AID - 12318 [pii]
AID - 10.18632/oncotarget.12318 [doi]
PST - ppublish
SO  - Oncotarget. 2016 Nov 15;7(46):75659-75671. doi: 10.18632/oncotarget.12318.