Two research teams have found that a molecule, which has been preserved throughout evolution and helps produce cholesterol, also plays a role in protecting cells from a type of cell death called ferroptosis. This discovery is important for medicine, as it could lead to new treatments for cancer and other diseases.
Ferroptosis is a form of controlled cell death that happens when iron causes fats in the cell membrane to oxidize, leading to damage. This results in mitochondrial shrinkage and cell swelling. Controlling ferroptosis could help treat conditions like kidney disease or neurodegenerative disorders, while inducing it could help kill cancer cells.The molecule 7-dehydrocholesterol (7-DHC), which is involved in making cholesterol, was found to block ferroptosis.
There are several enzymes that could potentially prevent ferroptosis, but the enzyme DHCR7 converts 7-DHC into cholesterol, which actually promotes ferroptosis. Because 7-DHC has a special structure that allows it to absorb harmful radicals and prevent lipid damage, it is considered a protective agent against ferroptosis.Ergosterol, found in yeast and fungi, is similar to 7-DHC and also protects against ferroptosis, suggesting that this defense mechanism may exist across different organisms.
This discovery could lead to breakthroughs in medicine. By adjusting 7-DHC levels, it may be possible to either prevent or trigger ferroptosis. Research by Freitas et al. found mutations in the DHCR7 gene in 9.8% of Burkitt’s lymphoma patients, with fewer mutations found in neuroblastoma patients. When the DHCR7 gene was deleted, 7-DHC levels increased, making neuroblastoma cells more resistant to ferroptosis, which caused tumors to grow and spread more rapidly.
Another study by Li et al. showed that inhibiting 7-DHC production with a molecule called TASIN-30 caused ferroptosis and suppressed tumor growth in mice. This happened even without other triggers of ferroptosis, highlighting the key role of 7-DHC in protecting some cancer cells from death.
Researchers also explored 7-DHC’s role in the spread of cancer. They found that this molecule helps melanoma cells survive and spread under oxidative stress. In a mouse model, blocking DHCR7 led to increased levels of 7-DHC, which protected kidney cells from ferroptosis.
These findings are rather new as they took place in January 2024, but are essential for the understanding of how to prevent ferroptosis. Drugs that target DHCR7 already exist, meaning this knowledge could lead to new treatments for diseases influenced by ferroptosis, though more research is needed to ensure safety, as excessive 7-DHC and its byproducts can harm the brain and eyes.
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