Superoxide-dependent and -independent mitochondrial signaling during apoptosis in multiple myeloma cells

Dharminder Chauhan; Guilan Li; Martin Sattler; Klaus Podar; Constantine Mitsiades; Nicholas Mitsiades; Nikhil Munshi; Teru Hideshima; Kenneth C Anderson

doi:10.1038/sj.onc.1206734

Superoxide-dependent and -independent mitochondrial signaling during apoptosis in multiple myeloma cells

Dharminder Chauhan, Guilan Li, Martin Sattler, Klaus Podar, Constantine Mitsiades, Nicholas Mitsiades, Nikhil Munshi, Teru Hideshima, Kenneth C Anderson

Research output: Journal article (peer-reviewed) › Journal article

53 Citations (Scopus)

Abstract

Superoxide (O ₂ ^-) radicals have been linked to apoptosis. Here, we show that 2-methoxyestradiol (2ME2)-induced apoptosis in multiple myeloma (MM) cells is associated with O ₂ ^- generation, whereas dexamethasone (Dex)-induced apoptosis occurs without concurrent increase in O ₂ ^-. In contrast, both these agents decrease mitochondrial transmembrane potential (Δψ _m). Treatment of MM cells with an antioxidant N-acetyl-L-cysteine blocks 2ME2, but not Dex-induced apoptosis as well as release of mitochondrial proteins cytochrome c (cyto c) and Smac. Taken together, these results demonstrate that there are at least two distinct apoptotic pathways: one dependent on O ₂ ^-, which is induced by 2ME2 and is associated with release of cyto c and Smac; and the other an independent of O ₂ ^-, which is triggered by Dex and associated with Smac release.

Original language	English
Pages (from-to)	6296-6300
Number of pages	5
Journal	Oncogene
Volume	22
Issue number	40
DOIs	https://doi.org/10.1038/sj.onc.1206734
Publication status	Published - 18 Sept 2003
Externally published	Yes

Keywords

2-Methoxyestradiol
Acetylcysteine
Antioxidants/pharmacology
Apoptosis/drug effects
Complement Membrane Attack Complex
Complement System Proteins
Cytochrome c Group/metabolism
Dexamethasone/pharmacology
Drug Resistance
Estradiol/analogs & derivatives
Glycoproteins/metabolism
Humans
Membrane Potentials/drug effects
Mitochondria/metabolism
Multiple Myeloma/genetics
Signal Transduction
Superoxides/metabolism
Tumor Cells, Cultured
Smac (second mitochondrial activator of caspases)
Multiple myeloma
2-methoxyestradiol
Dexamethasone
Superoxide
Cytochrome c
Apoptosis

ASJC Scopus subject areas

Genetics
Molecular Biology
Cancer Research

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10.1038/sj.onc.1206734

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title = "Superoxide-dependent and -independent mitochondrial signaling during apoptosis in multiple myeloma cells",

abstract = "Superoxide (O 2 -) radicals have been linked to apoptosis. Here, we show that 2-methoxyestradiol (2ME2)-induced apoptosis in multiple myeloma (MM) cells is associated with O 2 - generation, whereas dexamethasone (Dex)-induced apoptosis occurs without concurrent increase in O 2 -. In contrast, both these agents decrease mitochondrial transmembrane potential (Δψ m). Treatment of MM cells with an antioxidant N-acetyl-L-cysteine blocks 2ME2, but not Dex-induced apoptosis as well as release of mitochondrial proteins cytochrome c (cyto c) and Smac. Taken together, these results demonstrate that there are at least two distinct apoptotic pathways: one dependent on O 2 -, which is induced by 2ME2 and is associated with release of cyto c and Smac; and the other an independent of O 2 -, which is triggered by Dex and associated with Smac release. ",

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author = "Dharminder Chauhan and Guilan Li and Martin Sattler and Klaus Podar and Constantine Mitsiades and Nicholas Mitsiades and Nikhil Munshi and Teru Hideshima and Anderson, {Kenneth C}",

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doi = "10.1038/sj.onc.1206734",

language = "English",

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journal = "Oncogene",

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T1 - Superoxide-dependent and -independent mitochondrial signaling during apoptosis in multiple myeloma cells

AU - Chauhan, Dharminder

AU - Li, Guilan

AU - Sattler, Martin

AU - Podar, Klaus

AU - Mitsiades, Constantine

AU - Mitsiades, Nicholas

AU - Munshi, Nikhil

AU - Hideshima, Teru

AU - Anderson, Kenneth C

PY - 2003/9/18

Y1 - 2003/9/18

N2 - Superoxide (O 2 -) radicals have been linked to apoptosis. Here, we show that 2-methoxyestradiol (2ME2)-induced apoptosis in multiple myeloma (MM) cells is associated with O 2 - generation, whereas dexamethasone (Dex)-induced apoptosis occurs without concurrent increase in O 2 -. In contrast, both these agents decrease mitochondrial transmembrane potential (Δψ m). Treatment of MM cells with an antioxidant N-acetyl-L-cysteine blocks 2ME2, but not Dex-induced apoptosis as well as release of mitochondrial proteins cytochrome c (cyto c) and Smac. Taken together, these results demonstrate that there are at least two distinct apoptotic pathways: one dependent on O 2 -, which is induced by 2ME2 and is associated with release of cyto c and Smac; and the other an independent of O 2 -, which is triggered by Dex and associated with Smac release.

AB - Superoxide (O 2 -) radicals have been linked to apoptosis. Here, we show that 2-methoxyestradiol (2ME2)-induced apoptosis in multiple myeloma (MM) cells is associated with O 2 - generation, whereas dexamethasone (Dex)-induced apoptosis occurs without concurrent increase in O 2 -. In contrast, both these agents decrease mitochondrial transmembrane potential (Δψ m). Treatment of MM cells with an antioxidant N-acetyl-L-cysteine blocks 2ME2, but not Dex-induced apoptosis as well as release of mitochondrial proteins cytochrome c (cyto c) and Smac. Taken together, these results demonstrate that there are at least two distinct apoptotic pathways: one dependent on O 2 -, which is induced by 2ME2 and is associated with release of cyto c and Smac; and the other an independent of O 2 -, which is triggered by Dex and associated with Smac release.

KW - 2-Methoxyestradiol

KW - Acetylcysteine

KW - Antioxidants/pharmacology

KW - Apoptosis/drug effects

KW - Complement Membrane Attack Complex

KW - Complement System Proteins

KW - Cytochrome c Group/metabolism

KW - Dexamethasone/pharmacology

KW - Drug Resistance

KW - Estradiol/analogs & derivatives

KW - Glycoproteins/metabolism

KW - Humans

KW - Membrane Potentials/drug effects

KW - Mitochondria/metabolism

KW - Multiple Myeloma/genetics

KW - Signal Transduction

KW - Superoxides/metabolism

KW - Tumor Cells, Cultured

KW - Smac (second mitochondrial activator of caspases)

KW - Multiple myeloma

KW - 2-methoxyestradiol

KW - Dexamethasone

KW - Superoxide

KW - Cytochrome c

KW - Apoptosis

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U2 - 10.1038/sj.onc.1206734

DO - 10.1038/sj.onc.1206734

M3 - Journal article

C2 - 13679868

SN - 0950-9232

VL - 22

SP - 6296

EP - 6300

JO - Oncogene

JF - Oncogene

IS - 40

ER -

Superoxide-dependent and -independent mitochondrial signaling during apoptosis in multiple myeloma cells

Abstract

Keywords

ASJC Scopus subject areas

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