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Superoxide Dismutase As A Target For The Selective Killing Of Cancer Cells

P. Huang, L. Feng, E. Oldham, M. Keating, W. Plunkett
Published 2000 · Chemistry, Medicine

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Superoxide dismutases (SOD) are essential enzymes that eliminate superoxide radical (O2-) and thus protect cells from damage induced by free radicals. The active O2 - production and low SOD activity in cancer cells may render the malignant cells highly dependent on SOD for survival and sensitive to inhibition of SOD. Here we report that certain oestrogen derivatives selectively kill human leukaemia cells but not normal lymphocytes. Using complementary DNA microarray and biochemical approaches, we identify SOD as a target of this drug action and show that chemical modifications at the 2-carbon (2-OH, 2-OCH3) of the derivatives are essential for SOD inhibition and for apoptosis induction. Inhibition of SOD causes accumulation of cellular O2- and leads to free-radical-mediated damage to mitochondrial membranes, the release of cytochrome c from mitochondria and apoptosis of the cancer cells. Our results indicate that targeting SOD may be a promising approach to the selective killing of cancer cells, and that mechanism-based combinations of SOD inhibitors with free-radical-producing agents may have clinical applications.
This paper references
Kinetic study of O2− dismutation by bovine superoxide dismutase. Evidence for saturation of the catalytic sites by O2−
A. Rigo (1975)
Superoxide radicals and hydrogen peroxide formation in mitochondria from normal and neoplastic tissues.
O. Dionisi (1975)
Role of superoxide dismutase in cancer: a review.
L. Oberley (1979)
Bleomycin A2: a ferrous oxidase.
W. Caspary (1979)
The anthracycline antineoplastic drugs.
R. C. Young (1981)
Copper- and zinc-containing superoxide dismutase, manganese-containing superoxide dismutase, catalase, and glutathione peroxidase in normal and neoplastic human cell lines and normal human tissues.
S. Marklund (1982)
Superoxide-dependent formation of hydroxyl radicals and lipid peroxidation in the presence of iron salts. Detection of 'catalytic' iron and anti-oxidant activity in extracellular fluids.
J. Gutteridge (1982)
Free radicals in biology and medicine
B. Halliwell (1985)
DNA strand scission by enzymatically reduced mitomycin C: evidence for participation of the hydroxyl radical in the DNA damage.
K. Hamana (1985)
Termination of DNA synthesis by 9-beta-D-arabinofuranosyl-2-fluoroadenine. A mechanism for cytotoxicity.
P. Huang (1990)
Modification of DNA bases in mammalian chromatin by radiation-generated free radicals.
E. Gajewski (1990)
In vivo experimental studies on the role of free radicals in photodynamic therapy. I. Measurement of the steady state concentration of free radicals in tumor tissues of mice.
T. Shulyakovskaya (1993)
The endogenous oestrogen metabolite 2-methoxyoestradiol inhibits angiogenesis and suppresses tumour growth
T. Fotsis (1994)
2-Methoxyestradiol, an endogenous mammalian metabolite, inhibits tubulin polymerization by interacting at the colchicine site.
R. D'Amato (1994)
Synthesis, antitubulin and antimitotic activity, and cytotoxicity of analogs of 2-methoxyestradiol, an endogenous mammalian metabolite of estradiol that inhibits tubulin polymerization by binding to the colchicine binding site.
M. Cushman (1995)
Superoxide radical and superoxide dismutases.
I. Fridovich (1995)
Superoxide production in rat hippocampal neurons: selective imaging with hydroethidine
VP Bindokas (1996)
Spectrophotometric assay for superoxide dismutase based on tetrazolium salt 3'--1--(phenylamino)-carbonyl--3, 4-tetrazolium]-bis(4-methoxy-6-nitro)benzenesulfonic acid hydrate reduction by xanthine-xanthine oxidase.
H. Ukeda (1997)
In VivoExperimental Studies on the Role of Free Radicals in Photodynamic Therapy
D. Gál (1997)
Cytochrome c and dATP-Dependent Formation of Apaf-1/Caspase-9 Complex Initiates an Apoptotic Protease Cascade
Peng Li (1997)
Bcl-xL Regulates the Membrane Potential and Volume Homeostasis of Mitochondria
M. V. Heiden (1997)
A highly sensitive fluorescent micro-assay of H2O2 release from activated human leukocytes using a dihydroxyphenoxazine derivative.
J. Mohanty (1997)
Bax and adenine nucleotide translocator cooperate in the mitochondrial control of apoptosis.
I. Marzo (1998)
Superinduction of wild-type p53 protein after 2-methoxyestradiol treatment of Ad5p53-transduced cells induces tumor cell apoptosis
T. Mukhopadhyay (1998)
Redox gene therapy protects human IB-3 lung epithelial cells against ionizing radiation-induced apoptosis.
R. Zwacka (1998)
Manganese Superoxide Dismutase Mediates the Early Release of Mitochondrial Cytochrome C and Subsequent DNA Fragmentation after Permanent Focal Cerebral Ischemia in Mice
M. Fujimura (1999)
Oxygen insensitivity of the histochemical assay of glucose-6-phosphate dehydrogenase activity for the discrimination between nonmalignant and malignant cells.
B.E.M. van Driel (1999)
Superoxide anion inhibits drug‐induced tumor cell death
Shazib Pervaiz (1999)

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