DURHAM, N.C. A common compound known to fight lymphoma and skin conditions actually has a second method of action that makes it particularly deadly against certain aggressive breast tumors, researchers at Duke Medicine report.
The compound is called psoralen, a natural component found in foods such as figs and celery, and researchers have long understood that it that works by disrupting DNA replication and causing cell death when activated by an energy source such as UV light.
Duke researchers have now identified another way the compound works to kill tumor cells, raising the potential for psoralen to be developed as an effective therapy for cancers that are particularly vulnerable to this second mode of action.
Reporting in the Feb. 14, 2014 issue of the journal PLOS ONE, the researchers detail how psoralen blocks the signaling pathway of the HER2 receptor, which is overproduced in 25 percent of breast cancers, plus ovarian, gastric and other solid tumors. When HER2 is overproduced, it fuels uncontrolled cell growth, leading to an aggressive form of cancer. Psoralen shut down this process in experiments using HER2 overexpressing breast cancer cell lines.
"This was very unexpected," said senior author Neil L. Spector, M.D., the Sandra Coates Associate Professor of Medicine at Duke. "The therapy has been known to kill cancer cells by causing DNA damage, but it is also having a direct anti-tumor effect on HER2 overexpressing breast cancer cells by blocking HER2 signaling."
Psoralen also attacks another form of HER2 that is present in the nucleus of tumor cells. This form of the protein is resistant to cancer therapies such as lapatinib and trastuzumab that are otherwise effective in targeting HER2-positive cancers.
"Cancer drugs can recognize HER2 receptors when they are outside of the cell, but they don't recognize the truncated version inside the cell nucleus," Spector said. "We have shown that pso
|Contact: Sarah Avery|
Duke University Medical Center