Cancer cells are killed more effectively and selectively with a new approach, using a substance found in stinging nettles and ants, informs a study. Led by Professor Peter J Sadler from Warwick’s Department of Chemistry, researchers have developed a new line of attack against cancer: an organic-osmium compound, which is triggered using a non-toxic dose of sodium formate, a natural product found in many organisms, including nettles and ants.
Named JPC11, it targets a metabolic process which cancer cells rely on to survive and multiply. It does this by converting a key substance used by cancer cells to provide the energy they need for rapid division (pyruvate) into an unnatural lactate – leading to the cells’ destruction. Uniquely, this chemo-catalyst treatment can be recycled and reused within a cancer cell to attack it repeatedly.
This unprecedented functional ability to recycle and reuse the compound within cancer cells could lead to future anticancer drugs being administered in smaller, more effective, and potentially less toxic doses, decreasing the side-effects of chemotherapy. The researchers have been focussing on the potential to use this compound on ovarian and prostate cancers.
Importantly, the development opens up a possibility for a more selective cancer treatment as JPC11 was observed to specifically target the biochemistry of cancer cells, leaving healthy cells largely untouched – another improvement compared to existing platinum-based drugs, which can also attack non-cancerous cells.
Dr James Coverdale, Research Fellow, Warwick’s Department of Chemistry, said, “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. We have discovered that chemo-catalyst JPC11 has a unique mechanism of action – and we hope this will lead to more effective, selective and safer treatments in future.”
Professor Sadler commented, “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. Chemo-catalysts, especially those with immunogenic properties, might provide a breakthrough.”
Professor Martin Wills, catalyst specialist at University of Warwick, commented, “Although asymmetric catalytic hydrogenation processes are well developed in the materials industry, this research provides the first ever example of it being achieved inside cells using a synthetic catalyst.”
Handedness (molecular asymmetry) is critical to the function of bio-molecules in the body. Proteins, enzymes and our DNA, for example – are handed. Only the correct hand works, in the same way that a right hand does not fit a left-hand glove. In this case, the osmium compound JPC11, with sodium formate, can selectively produce a molecule of a specific ‘handedness’ – thus manipulating how cancer cells grow.
Dr Coverdale explained, “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, 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.”
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