Please use this identifier to cite or link to this item: https://doi.org/10.18632/oncotarget.12318
Title: Curcumin targets the TFEB-lysosome pathway for induction of autophagy
Authors: Zhang, J 
Wang, J 
Xu, J
Lu, Y
Jiang, J
Wang, L 
Shen, H.-M 
Xia, D
Keywords: curcumin
mammalian target of rapamycin
nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 1
protein kinase B
protein S6
transcription factor
transcription factor EB
unclassified drug
antineoplastic agent
basic helix loop helix leucine zipper transcription factor
curcumin
MTOR protein, human
protein binding
target of rapamycin kinase
TFEB protein, human
acidification
animal cell
antineoplastic activity
Article
autophagy
cell death
cell survival
concentration response
controlled study
drug mechanism
drug protein binding
embryo
enzyme activity
enzyme phosphorylation
enzyme repression
fibroblast
HCT116 cell line
human
human cell
lysosome
mouse
nonhuman
protein cleavage
protein expression
protein phosphorylation
animal
antagonists and inhibitors
autophagy
cell line
drug effects
gene knockout
genetics
HCT 116 cell line
lysosome
metabolism
signal transduction
transcription initiation
Animals
Antineoplastic Agents, Phytogenic
Autophagy
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Cell Line
Cell Survival
Curcumin
Fibroblasts
Gene Knockout Techniques
HCT116 Cells
Humans
Lysosomes
Mice
Protein Binding
Signal Transduction
TOR Serine-Threonine Kinases
Transcriptional Activation
Issue Date: 2016
Publisher: Impact Journals LLC
Citation: Zhang, J, Wang, J, Xu, J, Lu, Y, Jiang, J, Wang, L, Shen, H.-M, Xia, D (2016). Curcumin targets the TFEB-lysosome pathway for induction of autophagy. Oncotarget 7 (46) : 75659-75671. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.12318
Abstract: 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.
Source Title: Oncotarget
URI: https://scholarbank.nus.edu.sg/handle/10635/175451
ISSN: 19492553
DOI: 10.18632/oncotarget.12318
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