PMID- 22048238
OWN - NLM
STAT- MEDLINE
DCOM- 20120409
LR  - 20161125
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Linking)
VI  - 18
IP  - 1
DP  - 2012 Jan 1
TI  - Phenylarsine oxide induces apoptosis in Bax- and Bak-deficient cells through 
      upregulation of Bim.
PG  - 140-51
LID - 10.1158/1078-0432.CCR-10-3450 [doi]
AB  - PURPOSE: Bax and Bak are regarded as key mediators for cytochrome c (Cyt c) 
      release and apoptosis. Loss of Bax or Bak is often reported in human cancers and 
      renders resistance of these cancerous cells to chemotherapy. Here, we 
      investigated that phenylarsine oxide (PAO) could induce Bax/Bak-independent 
      apoptosis. EXPERIMENTAL DESIGN: Annexin V/propidium iodide (PI) staining, 
      terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) 
      staining, and caspase activation assays were conducted to detect apoptosis in 
      Bax/Bak-deficient mouse embryonic fibroblasts (MEF) and HCT116 bax(-/-) 
      colorectal cancer cells. Cyt c release and Bim expression were assessed by 
      Western blotting and immunostaining. Bim was stably knocked down by short hairpin 
      RNA. Immunoprecipitation was applied to detect the interaction between Bim and 
      Bcl-2. Both subcutaneous and colorectal orthotopic tumor implantation models were 
      used in nude mice to investigate the effect of PAO in vivo. RESULTS: PAO 
      triggered Cyt c release and apoptosis in a Bax/Bak-independent manner. Bim and 
      Bcl-2 were both involved in this process. PAO augmented the expression of Bim and 
      strengthened the interaction between Bim and Bcl-2. Furthermore, PAO attenuated 
      the growth of Bax-deficient cancer cells in vivo. CONCLUSIONS: Our results showed 
      that PAO induced apoptosis in chemotherapy-resistant cancer cells, which suggests 
      that PAO has the potential to serve as a chemotherapeutic agent for Bax- and 
      Bak-deficient cancers.
CI  - (c) 2011 AACR.
FAU - Ni, Biyun
AU  - Ni B
AD  - Joint Laboratory of Apoptosis and Cancer Biology, State Key Laboratory of 
      Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of 
      Sciences, Beijing, China.
FAU - Ma, Qi
AU  - Ma Q
FAU - Li, Baowei
AU  - Li B
FAU - Zhao, Lixia
AU  - Zhao L
FAU - Liu, Yong
AU  - Liu Y
FAU - Zhu, Yushan
AU  - Zhu Y
FAU - Chen, Quan
AU  - Chen Q
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111102
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Arsenicals)
RN  - 0 (BCL2L11 protein, human)
RN  - 0 (Bak1 protein, mouse)
RN  - 0 (Bax protein, mouse)
RN  - 0 (Bcl-2-Like Protein 11)
RN  - 0 (Bcl2l11 protein, mouse)
RN  - 0 (Membrane Proteins)
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (bcl-2 Homologous Antagonist-Killer Protein)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 0HUR2WY345 (oxophenylarsine)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Apoptosis Regulatory Proteins/genetics/*metabolism
MH  - Arsenicals/*pharmacology
MH  - Bcl-2-Like Protein 11
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Colorectal Neoplasms/drug therapy/metabolism/*pathology
MH  - Embryo, Mammalian/cytology/drug effects/metabolism
MH  - Fibroblasts/cytology/drug effects/metabolism
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Immunoprecipitation
MH  - Membrane Proteins/genetics/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Nude
MH  - Platelet Aggregation Inhibitors/*pharmacology
MH  - Proto-Oncogene Proteins/genetics/*metabolism
MH  - RNA, Messenger/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Up-Regulation
MH  - bcl-2 Homologous Antagonist-Killer Protein/*physiology
MH  - bcl-2-Associated X Protein/*physiology
EDAT- 2011/11/04 06:00
MHDA- 2012/04/10 06:00
CRDT- 2011/11/04 06:00
PHST- 2011/11/04 06:00 [entrez]
PHST- 2011/11/04 06:00 [pubmed]
PHST- 2012/04/10 06:00 [medline]
AID - 1078-0432.CCR-10-3450 [pii]
AID - 10.1158/1078-0432.CCR-10-3450 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2012 Jan 1;18(1):140-51. doi: 10.1158/1078-0432.CCR-10-3450. 
      Epub 2011 Nov 2.