The Pharoah’s Curse Once Killed Archaeologists. Now It Could Help Fight Cancer.

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The toxic fungus Aspergillus flavus—known as the “Pharaoh’s Curse” due to its role in the deaths of archaeologists who opened the Tomb of Tutankhamun in the 1920s—could have cancer-fighting abilities.
A new study developed ribosomally synthesized and post-translationally modified peptides (RiPPs), which produced novel structures of interlocking rings called “asperigimycins.”
When combined with a lipid, these asperigimycins disrupted cell division in leukemia cancer cells, and were as effective as FDA-approved therapies that have treated the disease for decades.

Fungi hold a prominent place in the history of medicine. Discovered in 1928, the world’s first antibiotic—penicillin–was derived from a simple mold, and since then, fungi have made their way into the ingredient lists of all kinds of immunosuppressants and cholesterol-lowering drugs. Some fungi with psychoactive properties are even being introduced in states across the U.S. as therapeutic tools.

However, not all fungi are medicinally helpful, and one of the more cursed members of the kingdom Fungi is Aspergillus flavus. A true microbial villain, this toxic fungus can produce aflatoxins, which can cause a variety of health issues and even death. The fungus garnered the cryptic nickname “Pharaoh’s Curse” due to it being linked to the deaths of several archeologists who opened ancient tombs around the world, including the famous discovery of the Tomb of Tutankhamun in the 1920s.

However, a new study published in the journal Nature Chemical Biology analyzes a wholly different aspect of this fungal villain—it’s cancer-fighting properties. The group of scientists led by researchers at the University of Pennsylvania (Penn) modified A. flavus and found molecules that formed a unique structure of interlocking rings, which they named “asperigimycins.”

When mixed with human leukemia cancer cells, these molecules—described as a class of ribosomally synthesized and post-translationally modified peptides, or RiPPs—were effective at knocking them out of commission. When the researchers added lipids (fatty molecules) to the mixture, the “Pharaoh’s Curse” transformed into a microbial blessing that worked as effectively as the FDA-approved drugs that’ve treated leukemia for decades.

“Fungi gave us penicillin,” Sherry Gao, senior author of the paper from Penn, said in a press statement. “These results show that many more medicines derived from natural products remain to be found.”

To better understand the properties of these RiPPs, the scientists selectively turned genes in the leukemia cells on and off. In doing so, they found that the SLC46A3 gene was crucial for the asperigimycins to enter the cancerous cells in enough numbers to be effective. The added lipid impacts how that gene transported chemicals into the cells, increasing their potency. However, the research team confirmed that these RiPPs were only useful against leukemia cells, and appeared to have no impact on breast, liver, or lung cancer cells. So, its usefulness is specific.

Once in the cells, the asperigimycins prevent cell division, which is the process by which cancer spreads. “Cancer cells divide uncontrollably,” Gao said in a press statement. “These compounds block the formation of microtubules, which are essential for cell division.”

The hope is to soon move testing of these compounds into animal models, and then continue onward to human trials in an effort to develop a new method of treating deadly cancers. “Nature has given us this incredible pharmacy,” Gao said in a press statement. “It’s up to us to uncover its secrets. As engineers, we’re excited to keep exploring, learning from nature and using that knowledge to design better solutions.”

What once was a pharaoh’s curse might one day turn out to be an oncologist’s blessing.

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