'Curse of Tutankhamun' Could Hide a Secret Cancer-Fighting Compound
The species, called Aspergillus flavus, is not actually a Pharaoh's curse, but it may be a medical blessing.
A new study, led by molecular engineers at the University of Pennsylvania (Upenn), has now found that this particular fungus possesses cancer-fighting compounds.
In the lab, when its natural products were mixed with human leukemia cancer cells, they showed potent effects. When modified, they even performed as well as some chemotherapy drugs.
The compounds are called RiPPs for short (ribosomally synthesized and post-translationally modified peptides), and they are made by a variety of organisms, including plants and bacteria.
In recent years, plant-derived RiPPS have shown great potential in fighting off some types of cancer, but fungal RiPPS are not as well researched and can be misidentified because of their unique structures.
"Even though only a few have been found, almost all of them have strong bioactivity," says lead author and biomolecular engineer Qiuyue Nie from UPenn. "This is an unexplored region with tremendous potential."
A. flavus is found around the world in decayed organic material, and its yellow-green spores can infect crops as well as the lungs of mammals. In humans, an aspergillosis infection can lead to chronic lung conditions that may be fatal if left untreated.
In 1973, some of the scientists who opened the tomb of a Polish King ended up dying prematurely. A microbiologist at the time found evidence of A. flavus in the tomb, which led to the assumption that this is what had killed the researchers.
This logic was then applied to the curious fates of workers and an earl who attended the opening of Egyptian pharaoh Tutankhamun's tomb in the early 20th century, only to famously die of illness days (or in the cases of the workers, years) later.
Aspergillus's role in these deaths has fuelled imaginations. But its rise to fame in the history books has brought the fungus scientific attention in the modern era.
Inspired by other studies which have linked A. flavus to anticancer activity, Nie and colleagues scanned a dozen different Aspergillus strains for RiPPs.
Using metabolic and genetic techniques, they zoomed in on four different purified compounds with similar, complex structures. They named them asperigimycins.
In lab experiments, two out of the the four asperigimycins exhibited high potency against leukemia cells, although none worked on breast, liver, or lung cancer cells.
When researchers modified one RiPP and added a fatty molecule (a lipid), the compound showed enhanced anti-cancer activity on several different leukemia cell lines and a breast cancer cell line.
In fact, this altered RiPP performed on par with two chemotherapy drugs approved by the FDA for leukemia: cytarabine and daunorubicin.
The authors of the study, who hail from a variety of institutions around the United States and Portugal, suspect that their lipid substitution affects how the activity of a specific gene allows the drug to better infiltrate and remain inside cancer cells, disrupting replication.
"Knowing that lipids can affect how this gene transports chemicals into cells gives us another tool for drug development," says Nie.
Nearly a century after fungi gave us penicillin, these curious lifeforms are pointing us in the direction of yet another potential advancement.
The study was published in Nature Chemical Biology.
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