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Researchers Identify Novel Target for Selective Killing of Cancer Cells

Researchers Identify Novel Target for Selective Killing of Cancer Cells
M. D. Anderson News Release 09/21/00

Scientists at The University of Texas M. D. Anderson Cancer Center have identified an essential enzyme as a novel target to kill cancer cells while sparing normal cells. 
 
Findings of the laboratory study demonstrate the effectiveness of inhibiting the essential enzyme - superoxide dismutase (SOD) - with the SOD inhibitor 2-methoxyestradiol (2-ME),  selectively prompting apoptosis, or programmed cell death in human leukemia cells but not in normal cells.  Results of the study have been published in the Sept. 21, 2000, issue of the journal Nature.

Human leukemia cells that responded to SOD inhibition in the laboratory include primary cancer cells from patients with chronic lymphocytic leukemia (CLL) and acute myelogenous leukemia (AML).

When SOD is present in healthy human cells, its function is to eliminate a certain free radical known as superoxide, which is toxic when accumulated in cells.  If a cell, however, becomes cancerous, errant mechanisms cause an abnormally active production of superoxide in the cell.  This makes the cancer cell more dependent on SOD to eliminate the toxic free radical, and thus more sensitive to inhibition of SOD.  In contrast, a normal cell, with its relatively low level of superoxide production and an intact regulatory mechanism, is able to tolerate a certain degree of SOD inhibition.  This means when normal and cancer cells are exposed to an appropriate dose of SOD inhibitor, the malignant cells die and normal cells are left intact.

Dr. Peng Huang, assistant professor of medicine in the Department of Experimental Therapeutics at M. D. Anderson, is principal investigator on the study.  In addition to the study showing promise in effectively killing leukemia cells, this new discovery also may provide a biochemical and molecular basis for the design of a new mechanism-based combination strategies to selectively kill cancer cells, according to Dr. Huang. In other laboratory studies 2-ME also has shown effectiveness in killing a variety of solid tumor cells, including ovarian and pancreatic cancer cells.

The SOD-targeting strategy has not yet been tested in persons with cancer.  Plans are under way for the next step in this research to evaluate the safety and effectiveness of 2-ME in clinical settings.

09/21/00


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