PMID- 22859272
OWN - NLM
STAT- MEDLINE
DCOM- 20130524
LR  - 20211203
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Linking)
VI  - 30
IP  - 4
DP  - 2012 Oct
TI  - Apoptosis induced by adenosine involves endoplasmic reticulum stress in EC109 
      cells.
PG  - 797-804
LID - 10.3892/ijmm.2012.1085 [doi]
AB  - Apoptosis plays a critical role in the development and homeostasis of 
      multicellular organisms, and endoplasmic reticulum stress (ERS) is one of the 
      intrinsic apoptosis pathways. Previous studies have shown that adenosine induces 
      apoptosis in several cancer cell lines. However, the molecular mechanism remains 
      poorly understood. In this study, we explored whether adenosine triggers 
      apoptosis of EC109 esophageal carcinoma (EC) cells by ERS. The MTT assay was used 
      to determine cell proliferation; cell cycle detection (FCM) and terminal 
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay were 
      performed to determine cell apoptosis. The subcellular distribution and 
      expression of the ERS-related proteins GRP78, cleaved caspase-3, cleaved 
      caspase-4, CHOP and NF-kappaB p65 were detected by western blot techniques. NF-kappaB 
      activation was measured by electrophoretic mobility shift assay (EMSA). The MTT 
      assay demonstrated that adenosine inhibited EC109 cell proliferation in a dose- 
      and time-dependent manner. FCM and TUNEL assay verified that adenosine caused an 
      apoptotic peak in cell cycle arrest and a higher percentage of apoptotic cells. 
      Western blot analysis confirmed that the expression of GRP78, cleaved caspase-4, 
      CHOP, NF-kappaB p65 and cleaved caspase-3 were upregulated in a dose-dependent manner 
      after adenosine treatment. EMSA revealed that adenosine activated NF-kappaB p65. This 
      is the first demonstration that adenosine inhibits cell proliferation, increases 
      GRP78 and NF-kappaB p65 expression and induces apoptosis by CHOP and caspase-4 
      pathways. The ERS pathway is involved in adenosine-induced apoptosis in EC109 
      cells.
FAU - Wu, Ling-Fei
AU  - Wu LF
AD  - Department of Gastroenterology, The Second Affiliated Hospital, Shantou 
      University Medical College, Shantou 515041, PR China. lingfeiwu@21cn.com
FAU - Wei, Bi-Liu
AU  - Wei BL
FAU - Guo, Yi-Tian
AU  - Guo YT
FAU - Ye, Yan-Qing
AU  - Ye YQ
FAU - Li, Guo-Ping
AU  - Li GP
FAU - Pu, Ze-Jin
AU  - Pu ZJ
FAU - Feng, Jia-Lin
AU  - Feng JL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120802
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (DDIT3 protein, human)
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - 0 (HSPA5 protein, human)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (NF-kappa B)
RN  - 147336-12-7 (Transcription Factor CHOP)
RN  - EC 3.4.22.- (CASP4 protein, human)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases, Initiator)
RN  - K72T3FS567 (Adenosine)
SB  - IM
MH  - Adenosine/*metabolism
MH  - *Apoptosis
MH  - Caspase 3/metabolism
MH  - Caspases, Initiator/metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Endoplasmic Reticulum Chaperone BiP
MH  - *Endoplasmic Reticulum Stress
MH  - Esophageal Neoplasms/*metabolism
MH  - Heat-Shock Proteins/metabolism
MH  - Humans
MH  - NF-kappa B/metabolism
MH  - Transcription Factor CHOP/metabolism
EDAT- 2012/08/04 06:00
MHDA- 2013/05/28 06:00
CRDT- 2012/08/04 06:00
PHST- 2012/06/02 00:00 [received]
PHST- 2012/07/23 00:00 [accepted]
PHST- 2012/08/04 06:00 [entrez]
PHST- 2012/08/04 06:00 [pubmed]
PHST- 2013/05/28 06:00 [medline]
AID - 10.3892/ijmm.2012.1085 [doi]
PST - ppublish
SO  - Int J Mol Med. 2012 Oct;30(4):797-804. doi: 10.3892/ijmm.2012.1085. Epub 2012 Aug 
      2.