Arsenic trioxide (As2O3) induces apoptosis through activation of Bax in hematopoietic cells

Yanhua Zheng, Hirohito Yamaguchi, Changhai Tian, Michael W. Lee, Hong Tang, Hong Gang Wang, Quan Chen

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

This study explores the roles of Bax and other Bcl-2 family members play in arsenic trioxide (As2O3)-induced apoptosis. We showed that As2O3 treatment triggered Bax conformational change and subsequent translocation from cytosol to mitochondria to form various multimeric homo-oligomers in IM-9 cells. On the other hand, human leukemic Jurkat cells deficient in Bax showed dramatically reduced apoptosis in response to As2O3. Stable overexpression of Bcl-2 in IM-9 cells (IM-9/Bcl-2) inhibited As2O3-mediated Bax activation and apoptosis, and this inhibition could be partially averted by cell-permeable Bid-Bcl-2 homology (BH)3 peptide. Meanwhile, Bax conformational change and oligomerization induced by As2O3 were not inhibited by the pancaspase inhibitor z-VAD-fmk, although Bid cleavage could be completely abolished. Bax activation by As2O3 seemed to require stress-induced intracelular reactive oxygen species (ROS), since the ROS scavengers (N-acetyl-L-cysteine and lipoic acid) could completely block the conformational change and translocation of Bax from cytosol to mitochondria. These data suggest that As2O3 might exert the cell killing in part by inducing Bax activation through a Bcl-2-suppressible pathway in hematopoietic cells that is caspase independent and intracellular ROS regulated.

Original languageEnglish (US)
Pages (from-to)3339-3347
Number of pages9
JournalOncogene
Volume24
Issue number20
DOIs
StatePublished - May 5 2005

Fingerprint

Apoptosis
Reactive Oxygen Species
Cytosol
Mitochondria
Thioctic Acid
Jurkat Cells
arsenic trioxide
Acetylcysteine
Caspases
Peptides

Keywords

  • Apoptosis
  • Arsenic trioxide
  • Bax
  • Mitochondria
  • Reactive oxygen species

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Zheng, Y., Yamaguchi, H., Tian, C., Lee, M. W., Tang, H., Wang, H. G., & Chen, Q. (2005). Arsenic trioxide (As2O3) induces apoptosis through activation of Bax in hematopoietic cells. Oncogene, 24(20), 3339-3347. https://doi.org/10.1038/sj.onc.1208484

Arsenic trioxide (As2O3) induces apoptosis through activation of Bax in hematopoietic cells. / Zheng, Yanhua; Yamaguchi, Hirohito; Tian, Changhai; Lee, Michael W.; Tang, Hong; Wang, Hong Gang; Chen, Quan.

In: Oncogene, Vol. 24, No. 20, 05.05.2005, p. 3339-3347.

Research output: Contribution to journalArticle

Zheng, Y, Yamaguchi, H, Tian, C, Lee, MW, Tang, H, Wang, HG & Chen, Q 2005, 'Arsenic trioxide (As2O3) induces apoptosis through activation of Bax in hematopoietic cells', Oncogene, vol. 24, no. 20, pp. 3339-3347. https://doi.org/10.1038/sj.onc.1208484
Zheng, Yanhua ; Yamaguchi, Hirohito ; Tian, Changhai ; Lee, Michael W. ; Tang, Hong ; Wang, Hong Gang ; Chen, Quan. / Arsenic trioxide (As2O3) induces apoptosis through activation of Bax in hematopoietic cells. In: Oncogene. 2005 ; Vol. 24, No. 20. pp. 3339-3347.
@article{d18a795aaff74a1fab8f61458ff25b5c,
title = "Arsenic trioxide (As2O3) induces apoptosis through activation of Bax in hematopoietic cells",
abstract = "This study explores the roles of Bax and other Bcl-2 family members play in arsenic trioxide (As2O3)-induced apoptosis. We showed that As2O3 treatment triggered Bax conformational change and subsequent translocation from cytosol to mitochondria to form various multimeric homo-oligomers in IM-9 cells. On the other hand, human leukemic Jurkat cells deficient in Bax showed dramatically reduced apoptosis in response to As2O3. Stable overexpression of Bcl-2 in IM-9 cells (IM-9/Bcl-2) inhibited As2O3-mediated Bax activation and apoptosis, and this inhibition could be partially averted by cell-permeable Bid-Bcl-2 homology (BH)3 peptide. Meanwhile, Bax conformational change and oligomerization induced by As2O3 were not inhibited by the pancaspase inhibitor z-VAD-fmk, although Bid cleavage could be completely abolished. Bax activation by As2O3 seemed to require stress-induced intracelular reactive oxygen species (ROS), since the ROS scavengers (N-acetyl-L-cysteine and lipoic acid) could completely block the conformational change and translocation of Bax from cytosol to mitochondria. These data suggest that As2O3 might exert the cell killing in part by inducing Bax activation through a Bcl-2-suppressible pathway in hematopoietic cells that is caspase independent and intracellular ROS regulated.",
keywords = "Apoptosis, Arsenic trioxide, Bax, Mitochondria, Reactive oxygen species",
author = "Yanhua Zheng and Hirohito Yamaguchi and Changhai Tian and Lee, {Michael W.} and Hong Tang and Wang, {Hong Gang} and Quan Chen",
year = "2005",
month = "5",
day = "5",
doi = "10.1038/sj.onc.1208484",
language = "English (US)",
volume = "24",
pages = "3339--3347",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "20",

}

TY - JOUR

T1 - Arsenic trioxide (As2O3) induces apoptosis through activation of Bax in hematopoietic cells

AU - Zheng, Yanhua

AU - Yamaguchi, Hirohito

AU - Tian, Changhai

AU - Lee, Michael W.

AU - Tang, Hong

AU - Wang, Hong Gang

AU - Chen, Quan

PY - 2005/5/5

Y1 - 2005/5/5

N2 - This study explores the roles of Bax and other Bcl-2 family members play in arsenic trioxide (As2O3)-induced apoptosis. We showed that As2O3 treatment triggered Bax conformational change and subsequent translocation from cytosol to mitochondria to form various multimeric homo-oligomers in IM-9 cells. On the other hand, human leukemic Jurkat cells deficient in Bax showed dramatically reduced apoptosis in response to As2O3. Stable overexpression of Bcl-2 in IM-9 cells (IM-9/Bcl-2) inhibited As2O3-mediated Bax activation and apoptosis, and this inhibition could be partially averted by cell-permeable Bid-Bcl-2 homology (BH)3 peptide. Meanwhile, Bax conformational change and oligomerization induced by As2O3 were not inhibited by the pancaspase inhibitor z-VAD-fmk, although Bid cleavage could be completely abolished. Bax activation by As2O3 seemed to require stress-induced intracelular reactive oxygen species (ROS), since the ROS scavengers (N-acetyl-L-cysteine and lipoic acid) could completely block the conformational change and translocation of Bax from cytosol to mitochondria. These data suggest that As2O3 might exert the cell killing in part by inducing Bax activation through a Bcl-2-suppressible pathway in hematopoietic cells that is caspase independent and intracellular ROS regulated.

AB - This study explores the roles of Bax and other Bcl-2 family members play in arsenic trioxide (As2O3)-induced apoptosis. We showed that As2O3 treatment triggered Bax conformational change and subsequent translocation from cytosol to mitochondria to form various multimeric homo-oligomers in IM-9 cells. On the other hand, human leukemic Jurkat cells deficient in Bax showed dramatically reduced apoptosis in response to As2O3. Stable overexpression of Bcl-2 in IM-9 cells (IM-9/Bcl-2) inhibited As2O3-mediated Bax activation and apoptosis, and this inhibition could be partially averted by cell-permeable Bid-Bcl-2 homology (BH)3 peptide. Meanwhile, Bax conformational change and oligomerization induced by As2O3 were not inhibited by the pancaspase inhibitor z-VAD-fmk, although Bid cleavage could be completely abolished. Bax activation by As2O3 seemed to require stress-induced intracelular reactive oxygen species (ROS), since the ROS scavengers (N-acetyl-L-cysteine and lipoic acid) could completely block the conformational change and translocation of Bax from cytosol to mitochondria. These data suggest that As2O3 might exert the cell killing in part by inducing Bax activation through a Bcl-2-suppressible pathway in hematopoietic cells that is caspase independent and intracellular ROS regulated.

KW - Apoptosis

KW - Arsenic trioxide

KW - Bax

KW - Mitochondria

KW - Reactive oxygen species

UR - http://www.scopus.com/inward/record.url?scp=18844384167&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=18844384167&partnerID=8YFLogxK

U2 - 10.1038/sj.onc.1208484

DO - 10.1038/sj.onc.1208484

M3 - Article

VL - 24

SP - 3339

EP - 3347

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 20

ER -