A family of chemicals naturally produced by fungi are phenomenally effective at killing human cancer cells, according to a study conducted by researchers from the Massachusetts Institute of Technology, the University of Illinois at Urbana-Champaign and published in the journal Chemical Science.
“What was particularly exciting to us was to see, across various cancer cell lines, that some of them are quite potent,” lead researcher Mohammad Movassaghi said.
The study was funded by the National Institute of General Medical Sciences.
Researchers have known for some time that a fungal chemical known as 11,11′-dideoxyverticillin demonstrates cancer fighting properties, but the chemical occurs in such small quantities that it was impossible to test its potency. Then a few years ago, MIT scientists successfully synthesized the chemical in the lab.
11,11′-dideoxyverticillin is just one of a family a fungal chemicals known as epipolythiodiketopiperazine (ETP) alkaloids. Scientists believe that fungi use ETP alkaloids to prevent other organisms from moving into the territory where they are living. In the new study, the researchers artificially synthesized 60 different ETP alkaloids and related chemicals in order to test them against different cancer lines.
“There’s a lot of data out there, very exciting data, but one thing we were interested in doing is taking a large panel of these compounds, and for the first time, evaluating them in a uniform manner,” Movassaghi said.
Alkaloids target cancer cells, ignore healthy ones
The researchers tested each of the 60 compounds against both lymphoma and cervical cancer, then took the 25 most effective chemicals and further tested them against breast, kidney and lung cancers. They found that the cancer-fighting chemicals were 1,000 times more likely to kill a cancer cell than they were to kill a healthy cell.
Because the scientists had manufactured all 60 chemicals by systematically varying specific parts of their underlying chemical structure, they were then able to isolate the chemical properties that make these fungal compounds most effective against cancer.
For example, the researchers found that two ETP molecules joined together were more effective than solitary ETP molecules, and that compounds containing two sulfur atoms were more effective than those containing fewer.
Significantly, the researchers were also able to identify portions of the fungal molecules that can be changed without producing any reduction in cancer-fighting effectiveness. This may help scientists turn the naturally occurring ETPs into more potent anti-cancer drugs, by replacing these “neutral” sections of the molecule with antibodies or other molecules designed to specifically deliver the ETP to a cancer cell.
The researchers now plan to use their findings to develop more precise cancer-fighting ETPs.
“We can go in with far greater precision and test the hypotheses we’re developing in terms of what portions of the molecules are most significant at retaining or enhancing biological activity,” Movassaghi said.
Numerous drugs currently on the market have been derived from fungi. The most famous of these is penicillin, the first modern antibiotic, which was derived in 1929 from a species of mold known as Penicillium rubens.