Scientists Discover Natural Compound That Stops Cancer Progression

Updated Tuesday 4 March 2025 15:0

A discovery led by OHSU was made possible by years of study conducted by University of Portland undergraduates.

Researchers have found a natural substance that can stop a crucial process in the development of several malignancies and demyelinating disorders, which harm the protective myelin coating that surrounds neurons, like multiple sclerosis (MS).

According to a study in the Journal of Biological Chemistry, sulfuretin, a flavonoid derived from plants, inhibits an enzyme that is connected to both cancer and multiple sclerosis. The study, which was carried out at Oregon Health & Science University using cell models, showed that sulfuretin successfully inhibited the activity of the enzyme. In order to assess the compound's therapeutic potential, efficacy, and potential adverse effects in the treatment of cancer and neurological illnesses like multiple sclerosis, the next stage of study will test it in animal models.

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A Potentially Wide-Reaching Treatment

Larry Sherman, Ph.D., a professor in the Division of Neuroscience at OHSU's Oregon National Primate Research Center, stated, "We believe this is a medication that could have an impact in a lot of different areas."

The researchers discovered that sulfuretin blocked the activity of a specific type of enzyme called a hyaluronidase, which naturally breaks down hyaluronic acid, as did two synthetic chemicals that were also examined in living cells. This is significant since fragments of hyaluronic acid have been shown to cause issues in at least two ways:

Prevents myelin repair: It stops oligodendrocytes, which are myelin-producing cells, from maturing. Each nerve cell's axon, the thread-like part of the cell that sends electrical messages between cells, is covered in a protective sheath called myelin. Multiple sclerosis, stroke, brain trauma, and some types of dementia are linked to myelin damage. Cerebral palsy or brain injury can also result from myelination delays in prematurely born babies.

Proliferates cancer cells: In malignant tumors, hyaluronidase activity may permit the growth of cancer cells without the inhibition of normal cellular death. Sherman, a professor of cell, developmental, and cancer biology at the OHSU School of Medicine, stated, "Now we have an inhibitor that could actually stop that."

The current study focuses on blocking cell migration-inducing and hyaluronan-binding protein, or CEMIP, a particular kind of hyaluronidase.

Apart from multiple sclerosis and cancer, CEMIP is linked to a number of illnesses, such as osteoarthritis, skin infections, excessive alcohol consumption-induced brain damage, and maybe other neurodevelopmental diseases including Alzheimer's disease. According to the study, sulfuretin seems to limit its function.

Flowers and their molecules

Co-author Angela Hoffman, Ph.D., a retired chemistry professor at the University of Portland, made the discovery after years of undergraduates laboriously screening plant chemicals in her lab.

“Over the years, her students have been grinding up these flowers, extracting molecules, and testing to see if any of them blocked hyaluronidase activity,” Sherman said. “Finally, a couple of years ago, they found a compound that was promising.”

Alec Peters, a graduate student in Sherman’s lab at OHSU, found that this compound blocked CEMIP activity in a tumor cell line and in oligodendrocyte progenitor cells. Oligodendrocytes generate myelin.

Hoffman, a nun and chemistry professor who earlier this year retired from the University of Portland after 35 years to lead her convent, began collaborating with Sherman a decade ago. Over that time, she said, hundreds of undergraduate students worked on breaking down dozens of plants to their molecular essence and then testing to see whether any of the compounds worked to neutralize CEMIP.

The new publication validates the students’ diligent work over many years, she said.

“Directing the students to be able to do this kind of research helps them in their careers,” Hoffman said. “This discovery could be useful for Alzheimer’s or other neurodegenerative conditions. As long as the underlying problem relates to hyaluronic acid being broken apart, this could be helpful for people.”

Reference: “Distinct chemical structures inhibit the CEMIP hyaluronidase and promote oligodendrocyte progenitor cell maturation” by Alec Peters, Fatima Banine, Kanon Yasuhara, Angela Hoffman, Prashant K. Basappa, Lily Metri, Ava Gunning, Jake Huffman, Clinton C. VanCampen, Stephen A. Shock and Larry S. Back, 24 October 2024, Journal of Biological Chemistry.
DOI: 10.1016/j.jbc.2024.107916

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