PMID- 24052408
OWN - NLM
STAT- MEDLINE
DCOM- 20140902
LR  - 20211203
IS  - 1573-675X (Electronic)
IS  - 1360-8185 (Linking)
VI  - 19
IP  - 1
DP  - 2014 Jan
TI  - Superoxide activates mTOR-eIF4E-Bax route to induce enhanced apoptosis in 
      leukemic cells.
PG  - 135-48
LID - 10.1007/s10495-013-0904-9 [doi]
AB  - Mammalian target of rapamycin (mTOR) is a central kinase that regulates cell 
      survival, proliferation and translation. Reactive oxygen species (ROS) are second 
      messengers with potential in manipulating cellular signaling. Here we report that 
      two ROS generating phytochemicals, hydroxychavicol and curcumin synergize in 
      leukemic cells in inducing enhanced apoptosis by independently activating both 
      mitogen activated protein kinase (MAPK) (JNK and P(38)) and mTOR pathways. Low 
      level transient ROS generated after co-treatment with these phytochemicals led to 
      activation of these two pathways. Both mTOR and MAPK pathways played important 
      roles in co-treatment-induced apoptosis, by knocking down either mTOR or MAPKs 
      inhibited apoptosis. Activation of mTOR, as evident from phosphorylation of its 
      downstream effector eukaryotic translation initiation factor 4E-binding protein 
      1, led to release of eukaryotic translation initiation factor 4E (eIF4E) which 
      was subsequently phosphorylated by JNK leading to translation of pro-apoptotic 
      proteins Bax and Bad without affecting the expression of anti-apoptotic protein 
      Bcl-xl. Our data suggest that mTOR and MAPK pathways converge at eIF4E in 
      co-treatment-induced enhanced apoptosis and provide mechanistic insight for the 
      role of mTOR activation in apoptosis.
FAU - Chaudhuri, Jaydeep
AU  - Chaudhuri J
AD  - Division of Cancer Biology and Inflammatory Disorder, Council of Scientific and 
      Industrial Research (CSIR)-Indian Institute of Chemical Biology (IICB), 4, Raja 
      S.C. Mullick Road, Jadavpur, Kolkata, 700032, India.
FAU - Chowdhury, Avik Acharya
AU  - Chowdhury AA
FAU - Biswas, Nabendu
AU  - Biswas N
FAU - Manna, Anirban
AU  - Manna A
FAU - Chatterjee, Saurav
AU  - Chatterjee S
FAU - Mukherjee, Tulika
AU  - Mukherjee T
FAU - Chaudhuri, Utpal
AU  - Chaudhuri U
FAU - Jaisankar, Parasuraman
AU  - Jaisankar P
FAU - Bandyopadhyay, Santu
AU  - Bandyopadhyay S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Apoptosis
JT  - Apoptosis : an international journal on programmed cell death
JID - 9712129
RN  - 0 (Eukaryotic Initiation Factor-4E)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 11062-77-4 (Superoxides)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - *Apoptosis
MH  - Eukaryotic Initiation Factor-4E/genetics/*metabolism
MH  - Humans
MH  - K562 Cells
MH  - Leukemia/enzymology/genetics/*metabolism/physiopathology
MH  - MAP Kinase Signaling System
MH  - Signal Transduction
MH  - Superoxides/*metabolism
MH  - TOR Serine-Threonine Kinases/genetics/*metabolism
MH  - Up-Regulation
MH  - bcl-2-Associated X Protein/genetics/*metabolism
EDAT- 2013/09/21 06:00
MHDA- 2014/09/03 06:00
CRDT- 2013/09/21 06:00
PHST- 2013/09/21 06:00 [entrez]
PHST- 2013/09/21 06:00 [pubmed]
PHST- 2014/09/03 06:00 [medline]
AID - 10.1007/s10495-013-0904-9 [doi]
PST - ppublish
SO  - Apoptosis. 2014 Jan;19(1):135-48. doi: 10.1007/s10495-013-0904-9.