PMID- 32278045
OWN - NLM
STAT- MEDLINE
DCOM- 20210422
LR  - 20211204
IS  - 1096-1186 (Electronic)
IS  - 1043-6618 (Linking)
VI  - 156
DP  - 2020 Jun
TI  - The anticancer effects of curcumin via targeting the mammalian target of 
      rapamycin complex 1 (mTORC1) signaling pathway.
PG  - 104798
LID - S1043-6618(20)31106-3 [pii]
LID - 10.1016/j.phrs.2020.104798 [doi]
AB  - The mammalian target of rapamycin (mTOR) is a protein kinase that has been 
      considered as a key regulator of a large number of cellular processes, including 
      cell growth, proliferation, differentiation, survival, and motility. 
      Overactivation of mTOR (especially mTORC1) signaling is related to oncogenic 
      cellular processes. Therefore targeting mTORC1 signaling is a new promising 
      strategy in cancer therapy. In this regard, various studies have shown that 
      curcumin, a polyphenol produced from the turmeric rhizome, has anti-inflammatory, 
      antioxidant and anticancer properties. Curcumin may exert its anticancer 
      function, at least in part, by suppressing mTOR-mediated signaling pathway in 
      tumor cells. However, the exact underlying mechanisms by which curcumin blocks 
      the mTORC1 signaling remain unclear. According to literature, curcumin inhibits 
      insulin-like growth factor 1 (IGF-1)/phosphoinositide 3-kinase (PI3K)/Akt/mTORC1 
      pathway which leads to apoptosis and cell cycle arrest via suppression of 
      erythroblastosis virus transcription factor 2 and murine double minute 2 
      oncoprotein. In addition, activation of unc-51-like kinase 1 by curcumin, as a 
      downstream target of IGF-1/PI3K/Akt/mTORC1 axis, enhances autophagy. Curcumin 
      induces AMP-activated protein kinase, a negative regulator of mTORC1, via 
      inhibition of F0F1-ATPase. Interestingly, curcumin suppresses IkappaB kinase beta, the 
      upstream kinase in mTORC1 pathway. Moreover, evidence revealed that curcumin 
      downregulates the E3-ubiquitin ligases NEDD4, neural precursor cell-expressed 
      developmentally downregulated 4. NEDD4 is frequently overexpressed in a wide 
      range of cancers and degrades the phosphatase and tensin homolog, which is a 
      negative regulator of mTORC1. Finally another suggested mechanism is suppression 
      of MAOA/mTORC1/hypoxia-inducible factor 1alpha signaling pathway by curcumin.
CI  - Copyright (c) 2020. Published by Elsevier Ltd.
FAU - Tamaddoni, Ahmad
AU  - Tamaddoni A
AD  - Non-Communicable Pediatric Diseases Research Center, Health Research Institute, 
      Babol University of Medical Sciences, Babol, Iran.
FAU - Mohammadi, Elahe
AU  - Mohammadi E
AD  - Department of Nutrition, Khalkhal University of Medical Sciences, Khalkhal, Iran. 
      Electronic address: a.mohammadi@khalums.ac.ir.
FAU - Sedaghat, Fatemeh
AU  - Sedaghat F
AD  - Department of Basic Medical Sciences, Faculty of Nutrition Sciences and Food 
      Technology, National Nutrition and Food Technology Research Institute, Shahid 
      Beheshti University of Medical Sciences, Tehran, Iran.
FAU - Qujeq, Durdi
AU  - Qujeq D
AD  - Cellular and Molecular Biology Research Center, Health Research Institute, Babol 
      University of Medical Sciences, Babol, Iran.
FAU - As'Habi, Atefeh
AU  - As'Habi A
AD  - Food Safety Research Center (Salt), Semnan University of Medical Sciences, 
      Semnan, Iran; Department of Nutrition, School of Nutrition and Food Sciences, 
      Semnan University of Medical Sciences, Semnan, Iran.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20200408
PL  - Netherlands
TA  - Pharmacol Res
JT  - Pharmacological research
JID - 8907422
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - IT942ZTH98 (Curcumin)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents, Phytogenic/*therapeutic use
MH  - Cell Proliferation/*drug effects
MH  - Curcumin/*therapeutic use
MH  - Humans
MH  - Mechanistic Target of Rapamycin Complex 1/*antagonists & inhibitors/metabolism
MH  - Neoplasms/*drug therapy/enzymology/pathology
MH  - Protein Kinase Inhibitors/*therapeutic use
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
OTO - NOTNLM
OT  - Cancer
OT  - Curcumin
OT  - mTOR
COIS- Declaration of Competing Interest The authors declare no conflicts of interest.
EDAT- 2020/04/12 06:00
MHDA- 2021/04/23 06:00
CRDT- 2020/04/12 06:00
PHST- 2019/12/22 00:00 [received]
PHST- 2020/03/26 00:00 [revised]
PHST- 2020/03/29 00:00 [accepted]
PHST- 2020/04/12 06:00 [pubmed]
PHST- 2021/04/23 06:00 [medline]
PHST- 2020/04/12 06:00 [entrez]
AID - S1043-6618(20)31106-3 [pii]
AID - 10.1016/j.phrs.2020.104798 [doi]
PST - ppublish
SO  - Pharmacol Res. 2020 Jun;156:104798. doi: 10.1016/j.phrs.2020.104798. Epub 2020 
      Apr 8.