flower-derived-compound-inhibits-enzyme-ms-cancer

Flower-Derived Compound Inhibits Key Enzyme Linked to Multiple Sclerosis and Cancer

Structures of flavonoids extracted from dahlia and coreopsis flowers. Red boxes denote similarities between compound structures and sulfuretin (A), while blue boxes denote differences.

Introduction

A natural compound has been identified by researchers to inhibit mechanisms underlying the progression of various cancers and demyelinating diseases, including multiple sclerosis, which affects the myelin sheath of neurons.

Key Findings of the Research

Sulfuretin: A Plant-Derived Flavonoid

Research published in the Journal of Biological Chemistry identifies sulfuretin, a plant-derived flavonoid, as an inhibitor of an enzyme linked to multiple sclerosis and cancer.

Discovery and Future Research

Researchers at Oregon Health & Science University (OHSU) discovered this compound in cell studies; next, they plan to test it in animal models to assess its potential efficacy and side effects for treating cancer and neurodegenerative diseases, including MS.

"We believe this compound could make a significant impact across various therapeutic fields," remarked Larry Sherman, Ph.D., professor in Neuroscience at OHSU's Oregon National Primate Research Center.

Mechanism of Action

Inhibition of Hyaluronidase

The researchers discovered that sulfuretin, along with two synthetic compounds tested in live cells, inhibited an enzyme called hyaluronidase, which naturally breaks down hyaluronic acid. This is significant as fragmented hyaluronic acid can lead to issues in at least two key ways:

1. Impeding Myelin Restoration

Impact on Oligodendrocytes: This compound impedes the maturation of oligodendrocytes, the cells responsible for producing myelin—the protective layer around each nerve cell's axon, which transmits electrical signals. Myelin damage is linked to MS, stroke, brain injuries, and some dementias. Delays in myelination may also affect premature infants, resulting in brain damage or cerebral palsy.

2. Promoting Cancer Cell Proliferation

Tumor Growth and Hyaluronidase Activity: In tumors, hyaluronidase activity may enable uncontrolled cancer cell growth by bypassing typical cell death processes. 'Now, we have an inhibitor that could potentially halt this,' noted Sherman, professor of cell, developmental, and cancer biology at OHSU School of Medicine.

Targeting CEMIP

The Role of CEMIP in Disease

The research aims to inhibit a particular hyaluronidase variant identified as cell migration-inducing and hyaluronan-binding protein, or CEMIP

CEMIP has been linked to several conditions in addition to MS and cancer, including osteoarthritis, skin infections, alcohol-related brain injury, and possibly other neurodevelopmental disorders, such as Alzheimer's disease. Findings indicate that sulfuretin appears to inhibit its function.

Chemical Compounds in Flowers

Research Journey and Student Involvement

This discovery resulted from years of diligent screening of plant compounds by undergraduate students in the laboratory of co-author Angela Hoffman, Ph.D., a former professor of chemistry at the University of Portland.

"For many years, her students have been processing these flowers by grinding them, extracting their molecules, and assessing whether any inhibit hyaluronidase activity," said Sherman. "Ultimately, a few years ago, they identified a compound with significant potential."

Contributions of Graduate Students

In Sherman's lab at OHSU, graduate student Alec Peters identified that this compound effectively blocked CEMIP activity in a tumor cell line as well as in oligodendrocyte progenitor cells, the cells that produce myelin.

A Legacy of Collaboration

Hoffman, a chemistry professor and nun, retired this year from the University of Portland after 35 years to take on leadership in her convent. She has collaborated with Sherman for the past decade, during which hundreds of undergraduates students have systematically broken down various plants to their molecular essence and evaluated the effectiveness of their compounds in neutralizing CEMIP.

The recent publication, she noted, confirms the students' persistent dedication and effort over many years.

Supporting Future Research

Hoffman expressed that supporting students in conducting this type of research contributes positively to their career advancement. She mentioned that the findings could be beneficial for Alzheimer's and other neurodegenerative ailments, as long as the issues stem from the degradation of hyaluronic acid.

Source

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