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Parthenolide, a compound derived from feverfew, a common garden plant, has the potential to provide an alternative treatment for chronic lymphocytic leukemia (CLL).
The most common adult leukemia, CLL typically affects patients over the age of 60, many of whom have comorbidities that prevent the use of aggressive chemotherapy. Additionally, because the disease eventually becomes resistant to treatment in some patients, there is a need to develop alternative, less aggressive treatment options.
Researchers led by Xingjian Li of the School of Chemistry at the University of Birmingham in the United Kingdom are focusing their efforts on parthenolide, a natural compound that has been found to exhibit anti-leukemic activity. Derived from a perennial flowering plant called feverfew, parthenolide has a sufficient bioavailability and can now be modified to produce multiple compounds that kill CLL cells.
The investigators extracted parthenolide from feverfew plants grown in the Winterbourne Botanic Garden at the University of Birmingham. The researchers modified the compound and determined that parthenolide can increase levels of reactive oxygen species in cells, thereby inducing oxidative stress and causing cell death. Parthenolide also targeted tumor cells by suppressing pro-survival and proliferation signaling through the pathway of NF-KB, a protein complex that regulates DNA transcription and cell survival. Additionally, by inhibiting NF-KB, parthenolide successfully reversed resistance to paclitaxel, oxaliplatin, doxorubicin, and a number of other chemotherapeutics used to treat CLL.
"This research is important not only because we have shown a way of producing parthenolide that could make it much more accessible to researchers," comments the study's corresponding author, John Fossey, PhD, Professor of Synthetic Chemistry at the University of Birmingham, "but also because we've been able to improve its 'drug-like' properties to kill cancer cells. It's a clear demonstration that parthenolide has the potential to progress from the flowerbed into the clinic."
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Image credit: H. Zell. Licensed under CC BY-SA 3.0