|
|
Prepublished online as a Blood First Edition Paper on January 16, 2003; DOI 10.1182/blood-2002-08-2512.
 Previous Article | Table of Contents | Next Article 
Blood, 15 May 2003, Vol. 101, No. 10, pp. 4098-4104
NEOPLASIA
Free radical stress in chronic lymphocytic leukemia cells and its
role in cellular sensitivity to ROS-generating anticancer
agents
Yan Zhou,
Elizabeth O. Hileman,
William Plunkett,
Michael J. Keating, and
Peng Huang
From the Departments of Molecular Pathology,
Experimental Therapeutics, and Leukemia, The University of Texas
M. D. Anderson Cancer Center, Houston, TX.
2-Methoxyestradiol (2-ME), a new anticancer agent currently in
clinical trials, has been demonstrated to inhibit superoxide dismutase
(SOD) and to induce apoptosis in leukemia cells through a free
radical-mediated mechanism. Because the accumulation of superoxide
(O2 ) by inhibition of SOD depends on the
cellular generation of O2, we hypothesized
that the endogenous production of superoxide may be a critical factor
that affects the antileukemia activity of 2-ME. In the present study,
we investigated the relationship between cellular
O2 contents and the cytotoxic activity of
2-ME in primary leukemia cells from 50 patients with chronic
lymphocytic leukemia (CLL). Quantitation of
O2 revealed that the basal cellular
O2 contents are heterogeneous among patients
with CLL. The O2 levels were significantly
higher in CLL cells from patients with prior chemotherapy. CLL cells
with higher basal O2 contents were more
sensitive to 2-ME in vitro than those with lower
O2 contents. There was a significant
correlation between the 2-ME-induced O2
increase and the loss of cell viability. Importantly, addition of
arsenic trioxide, a compound capable of causing reactive oxygen species
(ROS) generation, significantly enhanced the activity of 2-ME, even in
the CLL cells that were resistant to 2-ME alone. These results suggest
that the cellular generation of O2 plays an
important role in the cytotoxic action of 2-ME and that it is possible
to use exogenous ROS-producing agents such as arsenic trioxide in
combination with 2-ME to enhance the antileukemia activity and to
overcome drug resistance. Such a combination strategy may have
potential clinical applications.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
D. Trachootham, H. Zhang, W. Zhang, L. Feng, M. Du, Y. Zhou, Z. Chen, H. Pelicano, W. Plunkett, W. G. Wierda, et al.
Effective elimination of fludarabine-resistant CLL cells by PEITC through a redox-mediated mechanism
Blood,
September 1, 2008;
112(5):
1912 - 1922.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. E. Whibley, K. L. McPhail, R. A. Keyzers, M. F. Maritz, V. D. Leaner, M. J. Birrer, M. T. Davies-Coleman, and D. T. Hendricks
Reactive oxygen species mediated apoptosis of esophageal cancer cells induced by marine triprenyl toluquinones and toluhydroquinones
Mol. Cancer Ther.,
September 1, 2007;
6(9):
2535 - 2543.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Sharma, C. Joseph, S. Ghosh, A. Agarwal, M. K. Mishra, and E. Sen
Kaempferol induces apoptosis in glioblastoma cells through oxidative stress
Mol. Cancer Ther.,
September 1, 2007;
6(9):
2544 - 2553.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Ge, I. Montano, G. Rustici, W. J. Freebern, C. M. Haggerty, W. Cui, D. Ponciano-Jackson, G. V. R. Chandramouli, E. R. Gardner, W. D. Figg, et al.
Selective leukemic-cell killing by a novel functional class of thalidomide analogs
Blood,
December 15, 2006;
108(13):
4126 - 4135.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Zou, M. Adachi, K. Imai, M. Hareyama, K. Yoshioka, S. Zhao, and Y. Shinomura
2-Methoxyestradiol, an Endogenous Mammalian Metabolite, Radiosensitizes Colon Carcinoma Cells through c-Jun NH2-Terminal Kinase Activation.
Clin. Cancer Res.,
November 1, 2006;
12(21):
6532 - 6539.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Lemarie, C. Morzadec, D. Merino, O. Micheau, O. Fardel, and L. Vernhet
Arsenic Trioxide Induces Apoptosis of Human Monocytes during Macrophagic Differentiation through Nuclear Factor-{kappa}B-Related Survival Pathway Down-Regulation
J. Pharmacol. Exp. Ther.,
January 1, 2006;
316(1):
304 - 314.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S. Carew, S. T. Nawrocki, Y. V. Krupnik, K. Dunner Jr, D. J. McConkey, M. J. Keating, and P. Huang
Targeting endoplasmic reticulum protein transport: a novel strategy to kill malignant B cells and overcome fludarabine resistance in CLL
Blood,
January 1, 2006;
107(1):
222 - 231.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Hu, D. G. Rosen, Y. Zhou, L. Feng, G. Yang, J. Liu, and P. Huang
Mitochondrial Manganese-Superoxide Dismutase Expression in Ovarian Cancer: ROLE IN CELL PROLIFERATION AND RESPONSE TO OXIDATIVE STRESS
J. Biol. Chem.,
November 25, 2005;
280(47):
39485 - 39492.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. E. Sutherland, M. Schuliga, T. Harris, B. L. Eckhardt, R. L. Anderson, L. Quan, and A. G. Stewart
2-Methoxyestradiol Is an Estrogen Receptor Agonist That Supports Tumor Growth in Murine Xenograft Models of Breast Cancer
Clin. Cancer Res.,
March 1, 2005;
11(5):
1722 - 1732.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. D. Shanafelt, Y. K. Lee, N. D. Bone, A. K. Strege, V. L. Narayanan, E. A. Sausville, S. M. Geyer, S. H. Kaufmann, and N. E. Kay
Adaphostin-induced apoptosis in CLL B cells is associated with induction of oxidative stress and exhibits synergy with fludarabine
Blood,
March 1, 2005;
105(5):
2099 - 2106.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Qian, K. J. Liu, Y. Chen, D. C. Flynn, V. Castranova, and X. Shi
Cdc42 Regulates Arsenic-induced NADPH Oxidase Activation and Cell Migration through Actin Filament Reorganization
J. Biol. Chem.,
February 4, 2005;
280(5):
3875 - 3884.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Pelicano, L. Feng, Y. Zhou, J. S. Carew, E. O. Hileman, W. Plunkett, M. J. Keating, and P. Huang
Inhibition of Mitochondrial Respiration: A NOVEL STRATEGY TO ENHANCE DRUG-INDUCED APOPTOSIS IN HUMAN LEUKEMIA CELLS BY A REACTIVE OXYGEN SPECIES-MEDIATED MECHANISM
J. Biol. Chem.,
September 26, 2003;
278(39):
37832 - 37839.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
