A compound found in stinging nettles may help in the fight against cancer.
A platinum-based drug called cisplatin is often used in the fight against cancer. Though it can be effective, there are significant shortfalls.
Over time, many cancers become resistant to the drug, and its ability to kill cancer cells diminishes.
Another issue is that cisplatin attacks healthy as well as cancerous cells, leading to a range of side effects.
For these reasons and others, more efficient cancer treatments are constantly being searched for.
Researchers at the University of Warwick in the United Kingdom recently studied a new compound to assess whether it might be useful in the fight against cancer, particularly ovarian cancer and prostate cancer.
Prof. Peter Sadler, a medicinal chemist from the University of Warwick, explains their focus, saying, “Platinum compounds are the most widely used drugs for cancer chemotherapy, but we urgently need to respond to the challenges of circumventing resistance and side effects.”
“Our lab,” he continues, “is focused on the discovery of truly novel anti-cancer drugs which can kill cells in totally new ways. Chemo-catalysts, especially those with immunogenic properties, might provide a breakthrough.”
The results of the team’s experiments are published this week in the journal Nature Chemistry.
A new road to explore
The laboratory’s latest chemical of interest is JPC11, an organic-osmium compound. This chemical is reusable, meaning that it can attack cancer a number of times.
Once in the body, JPC11 is triggered by a “non-toxic dose of sodium formate,” a naturally occurring compound found in ants and stinging nettles.
JPC11 impairs cancer cells by meddling with vital metabolic processes. Cancer cells require energy to divide rapidly, and they derive this from pyruvate. JPC11 turns pyruvate into an unnatural lactate that cancer cells cannot use, effectively killing them off.
Because a single dose of JPC11 attacks cancer repeatedly, it is hoped that this type of technology might lead to treatments that require lower overall doses, thereby minimizing side effects.
Another benefit of JPC11 over traditional treatment is that it specifically targets cancer cells, leaving healthy tissue relatively untouched.
“This is a significant step in the fight against cancer. Manipulating and applying well-established chemistry in a biological context provides a highly selective strategy for killing cancer cells.”
Dr. James Coverdale, University of Warwick’s Department of Chemistry
“We have discovered,” adds Dr. Coverdale, “that chemo-catalyst JPC11 has a unique mechanism of action — and we hope that this will lead to more effective, selective, and safer treatments in the future.”
The importance of handedness
JPC11 achieves its cancer-killing skills by meddling in molecular symmetry, which is otherwise known as handedness, or chirality.
An example of molecular handedness in a generic amino acid.
Two chemicals can be constructed in the same shape with the same atoms, but be a mirror image and respond differently in certain chemical situations.
A number of biological compounds — enzymes, proteins, and DNA, for instance — are handed, and only the correct hand works. In the same way that a right-hand glove will not fit on the left hand, the handedness of a molecule changes its property.
When sodium formate, the stinging nettle compound, interacts with JPC11, it produces molecules of a specific handedness, altering the way that cancer cells grow.
As Dr. Coverdale explains, “The ‘handedness’ of molecules is critical in the body. Our hands are near-identical but are mirror images of each other.”
“The same can be true of molecules,” he adds, “and in some cases, having the wrong-handed molecule can have profound biological consequences. We believe that manipulation of the ‘handedness’ of molecules in cells could provide a new strategy for fighting diseases.”
As with any experimental drug, a great deal of work is needed before it can be used in patients. Prof. Sadler is confident that the University of Warwick team are well-placed to push it forward.
He notes, “It will take time to progress from the lab to the clinic, but we are fortunate to have a talented, enthusiastic, international team working with colleagues in Warwick Cancer Research Centre across the borderlines of chemistry, cell and systems biology, and cancer medicine who are determined to succeed.”
Any discovery in oncology sparks interest in the medical community at large, and this advance is no different. The team hopes that manipulating the handedness of molecules could offer an entirely new strategy for fighting disease.
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