Scientists have identified a natural compound with potential to halt the progression of specific cancers and demyelinating diseases like multiple sclerosis (MS), which damages the protective myelin sheath surrounding neurons. According to a study published today in the Journal of Biological Chemistry, a plant-derived flavonoid called sulfuretin effectively blocked an enzyme associated with MS and cancer during tests on cells in an Oregon Health & Science University (OHSU) lab. Researchers plan to further investigate sulfuretin’s potential in animal models to assess its effectiveness and any side effects in treating these diseases.
“This is a compound that could have a wide-ranging impact,” said Larry Sherman, Ph.D., professor of neuroscience at OHSU’s Oregon National Primate Research Center.
In the study, sulfuretin and two synthetic compounds were found to inhibit a specific enzyme, hyaluronidase, which naturally breaks down hyaluronic acid. This is significant because the breakdown of hyaluronic acid can disrupt myelin repair and foster cancer growth:
1. Impacts Myelin Repair: Hyaluronic acid fragments can prevent oligodendrocytes, cells responsible for producing myelin, from maturing properly. Myelin serves as a protective sheath around nerve cells, facilitating electrical signals between neurons. When myelin is damaged, it can lead to MS, strokes, brain injuries, and some forms of dementia. In newborns, delayed myelination may lead to brain damage or cerebral palsy.
2. Promotes Cancer Cell Growth: In cancerous tumors, hyaluronidase activity enables cancer cells to multiply unchecked, evading normal cell death. Sherman explained, “We now have an inhibitor that could potentially stop that.”
This research zeroes in on a hyaluronidase known as cell migration-inducing hyaluronan-binding protein (CEMIP), implicated in several diseases beyond MS and cancer, including osteoarthritis, skin infections, brain injury from alcohol use, and potentially Alzheimer’s disease. Findings from the study suggest sulfuretin may inhibit CEMIP activity, opening possibilities for treatments targeting various neurodegenerative conditions.
The discovery stemmed from years of meticulous screening of plant compounds in the lab of Angela Hoffman, Ph.D., a retired chemistry professor at the University of Portland. Hoffman’s undergraduate students spent years grinding and extracting molecules from plants to identify those that block hyaluronidase. Their work paid off when they finally identified a promising compound.
Alec Peters, a graduate student in Sherman’s lab, found that this compound effectively blocked CEMIP activity in both a tumor cell line and oligodendrocyte progenitor cells — the cells responsible for generating myelin.
Hoffman, a nun and former chemistry professor who recently retired to lead her convent, has collaborated with Sherman for over a decade. Hundreds of students contributed to this research, breaking down plant material and testing for compounds that neutralize CEMIP. Hoffman reflected on the significance of her students’ efforts, noting, “This discovery could also be beneficial for Alzheimer’s or other neurodegenerative conditions. Any condition related to hyaluronic acid degradation may benefit from this.”
The study was supported by grants from the National Institutes of Health, Congressionally Directed Medical Research Programs, the National Multiple Sclerosis Society, and the National Institute of Neurological Disorders and Stroke. While these grants funded the research, the content does not necessarily reflect the views of the NIH.
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