Scientists at Fred Hutchinson Cancer Research Center report that a modified version of antimycin, called 2-Methoxy antimycin, is selective in killing cells that have high levels of Bcl-2 and Bcl-xL proteins. The over expression of these proteins in many types of cancer cells correlates with resistance to chemotherapy and radiation therapy, according to the team. Cells with normal levels of Bcl-2 or Bcl-xL are resistant to 2-Methoxy antimycin.
“Our compound, 2-Methoxy antimycin, is the only Bcl-2 inhibitor reported with gain of function activity, which provides a therapeutic window between cancer cells with high expression of the proteins versus cells with normal expression,” says David M. Hockenbery, M.D., principle investigator and a professor of medicine at the University of Washington Medical Center. “This effect was preserved when 2-Methoxy antimycin was used in combination with other agents and could lead to a targeted molecular therapy to enhance the effectiveness of cancer treatments.”
The researchers set up screening assays to look for small molecules or compounds that are selectively toxic to cells that over express Bcl-2 proteins. They found that higher expression of the target protein made cells more sensitive to the 2-Methoxy antimycin inhibitor.
The paper was published in the July 11 issue of Molecular Cancer Therapeutics.