PMID- 21745187
OWN - NLM
STAT- MEDLINE
DCOM- 20111125
LR  - 20131121
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 439
IP  - 3
DP  - 2011 Nov 1
TI  - Adaphostin promotes caffeine-evoked autocrine Fas-mediated death pathway 
      activation in Bcr/Abl-positive leukaemia cells.
PG  - 453-67
LID - 10.1042/BJ20110725 [doi]
AB  - The present study was conducted to verify whether caffeine is beneficial for 
      improving leukaemia therapy. Co-treatment with adaphostin (a Bcr/Abl inhibitor) 
      was found to potentiate caffeine-induced Fas/FasL up-regulation. Although 
      adaphostin did not elicit ASK1 (apoptosis signal-regulating kinase 1)-mediated 
      phosphorylation of p38 MAPK (mitogen-activated protein kinase) and JNK (c-Jun 
      N-terminal kinase), co-treatment with adaphostin notably increased p38 MAPK/JNK 
      activation in caffeine-treated cells. Suppression of p38 MAPK and JNK abrogated 
      Fas/FasL up-regulation in caffeine- and caffeine/adaphostin-treated cells. 
      Compared with caffeine, adaphostin markedly suppressed Akt/ERK 
      (extracellular-signal-regulated kinase)-mediated MKP-1 (MAPK phosphatase 1) 
      protein expression in K562 cells. MKP-1 down-regulation eventually elucidated the 
      enhanced effect of adaphostin on p38 MAPK/JNK activation and subsequent Fas/FasL 
      up-regulation in caffeine-treated cells. Knockdown of p38alpha MAPK and JNK1, ATF-2 
      (activating transcription factor 2) and c-Jun by siRNA (small interfering RNA) 
      proved that p38alpha MAPK/ATF-2 and JNK1/c-Jun pathways were responsible for 
      caffeine-evoked Fas/FasL up-regulation. Moreover, Ca2+ and ROS (reactive oxygen 
      species) were demonstrated to be responsible for ASK1 activation and Akt/ERK 
      inactivation respectively in caffeine- and caffeine/adaphostin-treated cells. 
      Likewise, adaphostin functionally enhanced caffeine-induced Fas/FasL 
      up-regulation in leukaemia cells that expressed Bcr/Abl. Taken together, the 
      results of the present study suggest a therapeutic strategy in improving the 
      efficacy of adaphostin via Fas-mediated death pathway activation in 
      Bcr/Abl-positive leukaemia.
FAU - Liu, Wen-Hsin
AU  - Liu WH
AD  - Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, 
      Taiwan.
FAU - Chang, Long-Sen
AU  - Chang LS
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Fas Ligand Protein)
RN  - 0 (Hydroquinones)
RN  - 0 (NSC 680410)
RN  - 0 (abl-bcr fusion protein, human)
RN  - 3G6A5W338E (Caffeine)
RN  - EC 2.7.10.2 (Fusion Proteins, bcr-abl)
RN  - PJY633525U (Adamantane)
SB  - IM
MH  - Adamantane/*analogs & derivatives/pharmacology
MH  - Autocrine Communication/drug effects/*physiology
MH  - Caffeine/*pharmacology
MH  - Fas Ligand Protein/*physiology
MH  - Fusion Proteins, bcr-abl/*antagonists & inhibitors/*metabolism
MH  - Humans
MH  - Hydroquinones/*pharmacology
MH  - K562 Cells
MH  - MAP Kinase Signaling System/*drug effects/physiology
MH  - U937 Cells
EDAT- 2011/07/13 06:00
MHDA- 2011/12/13 00:00
CRDT- 2011/07/13 06:00
PHST- 2011/07/13 06:00 [entrez]
PHST- 2011/07/13 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
AID - BJ20110725 [pii]
AID - 10.1042/BJ20110725 [doi]
PST - ppublish
SO  - Biochem J. 2011 Nov 1;439(3):453-67. doi: 10.1042/BJ20110725.