PMID- 23712032
OWN - NLM
STAT- MEDLINE
DCOM- 20140303
LR  - 20171116
IS  - 1873-3913 (Electronic)
IS  - 0898-6568 (Linking)
VI  - 25
IP  - 10
DP  - 2013 Oct
TI  - Activation of AMP-activated protein kinase (AMPK) mediates plumbagin-induced 
      apoptosis and growth inhibition in cultured human colon cancer cells.
PG  - 1993-2002
LID - S0898-6568(13)00157-5 [pii]
LID - 10.1016/j.cellsig.2013.05.026 [doi]
AB  - Here we report that activation of AMP-activated protein kinase (AMPK) mediates 
      plumbagin-induced apoptosis and growth inhibition in both primary cultured human 
      colon cancer cells and cell lines. Knocking-down of AMPKalpha by the target shRNA 
      significantly inhibits plumbagin-induced cytotoxicity in cultured colon cancer 
      cells, while forced activation of AMPK by introducing a constitutively active 
      AMPK (CA-AMPK), or by the AMPK activator, inhibits HT-29 colon cancer cell 
      growth. Our Western-blots and immunoprecipitation (IP) results demonstrate that 
      plumbagin induces AMPK/Apoptosis signal regulating kinase 1 (ASK1)/TNF 
      receptor-associated factor 2 (TRAF2) association to activate pro-apoptotic c-Jun 
      N-terminal kinases (JNK)-p53 signal axis. Further, after plumbagin treatment, 
      activated AMPK directly phosphorylates Raptor to inhibit mTOR complex 1 (mTORC1) 
      activation and Bcl-2 expression in colon cancer cells. Finally, we found that 
      exogenously-added short-chain ceramide (C6) enhances plumbagin-induced AMPK 
      activation and facilitates cell apoptosis and growth inhibition. Our results 
      suggest that AMPK might be the key mediator of plumbagin's anti-tumor activity.
CI  - Copyright (c) 2013. Published by Elsevier Inc.
FAU - Chen, Min-Bin
AU  - Chen MB
AD  - Department of Medical Oncology, Kunshan First People's Hospital Affiliated to 
      Jiangsu University, 91 Qianjin Road, Kunshan 215300, Jiangsu Province, China.
FAU - Zhang, Yan
AU  - Zhang Y
FAU - Wei, Mu-Xin
AU  - Wei MX
FAU - Shen, Wei
AU  - Shen W
FAU - Wu, Xiao-Yang
AU  - Wu XY
FAU - Yao, Chen
AU  - Yao C
FAU - Lu, Pei-Hua
AU  - Lu PH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130525
PL  - England
TA  - Cell Signal
JT  - Cellular signalling
JID - 8904683
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Naphthoquinones)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - YAS4TBQ4OQ (plumbagin)
SB  - IM
MH  - AMP-Activated Protein Kinases/antagonists & inhibitors/genetics/*metabolism
MH  - Antineoplastic Agents, Phytogenic
MH  - Apoptosis/*genetics
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Colonic Neoplasms/genetics/*metabolism/pathology
MH  - Gene Expression Regulation, Neoplastic
MH  - HT29 Cells
MH  - Humans
MH  - Naphthoquinones/metabolism
MH  - Phosphorylation
MH  - Primary Cell Culture
MH  - Reactive Oxygen Species/*metabolism
MH  - Signal Transduction/genetics
OTO - NOTNLM
OT  - 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside
OT  - ACC
OT  - AICAR
OT  - AMP-activated protein kinase
OT  - AMP-activated protein kinase (AMPK)
OT  - AMPK
OT  - ASK1
OT  - Colon cancer
OT  - FACS
OT  - IP
OT  - JNK
OT  - NAC
OT  - PI
OT  - Plumbagin
OT  - RNA interference
OT  - RNAi
OT  - ROS
OT  - Raptor
OT  - S6K1
OT  - TNF receptor-associated factor 2
OT  - TRAF2
OT  - TSC2
OT  - UA
OT  - acetyl-CoA carboxylase
OT  - apoptosis signal regulating kinase 1
OT  - c-Jun N-terminal kinase
OT  - fluorescence-activated cell sorting
OT  - immunoprecipitation
OT  - mTOR complex 1
OT  - mTORC1
OT  - n-acetyl-l-cysteine
OT  - propidium iodide
OT  - reactive oxygen species
OT  - regulatory associated protein of mTOR
OT  - ribosomal p70 S6 kinase
OT  - tuberous sclerosis protein 2
OT  - ursolic acid
EDAT- 2013/05/29 06:00
MHDA- 2014/03/04 06:00
CRDT- 2013/05/29 06:00
PHST- 2013/03/21 00:00 [received]
PHST- 2013/05/18 00:00 [accepted]
PHST- 2013/05/29 06:00 [entrez]
PHST- 2013/05/29 06:00 [pubmed]
PHST- 2014/03/04 06:00 [medline]
AID - S0898-6568(13)00157-5 [pii]
AID - 10.1016/j.cellsig.2013.05.026 [doi]
PST - ppublish
SO  - Cell Signal. 2013 Oct;25(10):1993-2002. doi: 10.1016/j.cellsig.2013.05.026. Epub 
      2013 May 25.