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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 |
Appears in Collections: | Staff Publications Elements |
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