Scientists have identified a synthetic compound that effectively targets leukemia cells while sparing healthy blood cells. The molecule, named Orpinolide, was inspired by natural compounds found in nightshade plants and works by disrupting cholesterol transport in cancer cells.
From Toxic Plants to Cancer Treatment
Nightshade plants are known for their diverse array of compounds, some toxic and others with potential medical applications. A class of steroids called Withanolides, produced by these plants, has shown promise for their anti-inflammatory, antioxidant, and cancer-preventive properties.
Researchers at the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, collaborating with the Max Planck Institute for Molecular Physiology, screened artificial variants of Withanolides against chronic myeloid leukemia and T-cell leukemia cells. Their efforts led to the discovery of Orpinolide, a compound that selectively kills tumor cells while minimally affecting non-malignant blood cells.
Unraveling Orpinolide’s Mechanism
Using advanced techniques like quantitative proteomics, transcriptomics, and CRISPR/Cas9 gene editing, the team identified how Orpinolide works. The molecule binds to and inhibits OSBP, a protein responsible for cholesterol transport in cells.
Study lead Georg Winter explained, “This study highlights sterol transport as an Achilles’ heel in leukemia, one that we can block with chemical agents.”
Lead author Marko Cigler added, “Natural substances remain an important source of inspiration for new drugs. Our ability to comprehensively understand them should open numerous possibilities for future innovations in drug research.”
The research, published in Nature Chemical Biology, demonstrates the potential of targeting cholesterol metabolism in cancer cells and could pave the way for new leukemia treatments.
Additional Resources:
Here are three additional resources to learn more about the topics covered in the article:
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Overview of nightshade plants and their compounds:
- “National Institutes of Health” provides a general overview of nightshade plants, including a section on their chemical constituents.
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Basics of cholesterol transport in cells:
- “Khan Academy: Cholesterol Transport” offers an easy-to-understand explanation of cholesterol transport within cells, complete with visuals.
- Current treatments for chronic myeloid leukemia and T-cell leukemia:
- “American Cancer Society: Chronic Myeloid Leukemia Treatment” and “American Cancer Society: T-Cell Leukemia Treatment” provide detailed information on treatment options for these specific leukemia types.
