More than just a pain – catalyst triggered by ‘stinging nettle’ compound could tackle tough cancers
New approach uses natural product found in stinging nettles, sodium formate, to trigger reduction of pyruvate in ovarian cancer cells, preventing cell division.
In their recent paper published in Nature Chemistry, a team lead by Peter Sadler, Professor of Chemistry at the University of Warwick (United Kingdom), have developed JPC11, a synthetic complex that acts as a catalyst to reduce pyruvate and prevent cell metabolism. The complex, which is activated in the presence of sodium formate, selectively targets the metabolism of cancer cells. Researchers hope that this treatment could be used to target ovarian and other hard-to-treat cancers, using smaller and less toxic doses.
Despite being one of the most widely used drugs, the use of cisplatin for cancer treatment is not always effective as it is prone to fast build-up of resistance in tumors and has debilitating side effects due to its cytotoxicity. In recent years there has been significant effort to develop novel methods for tackling cancers which standard chemotherapy fails to deal with, such as ovarian and prostate cancer.
In their new work, Sadler and his team have designed an osmium compound which acts to catalyze the asymmetric transfer hydrogenation of pyruvate to achieve enantiomeric reduction. After the reduction of pyruvate, the complex is recycled in the presence of sodium formate, a natural product found in stinging nettles and some ants. As a key metabolic intermediate, the removal of pyruvate halts several vital chemical pathways, preventing cell division.
Importantly, the complex specifically targets the metabolism of cancerous cells. The selectivity of the compound and its catalytic nature mean that this treatment could require smaller doses than standard chemotherapy, reducing side effects and sidestepping tumor resistance to cisplatin. Research fellow James Coverdale (University of Warwick, United Kingdom) stated: “We have discovered 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.”
Sadler is confident that the research could lead to an urgently needed new class of anti-cancer treatments, explaining: “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 is focused on the discovery of truly novel anticancer drugs which can kill cells in totally new ways. Chemo-catalysts, especially those with immunogenic properties, might provide a breakthrough.”
Coverdale J, Romero-Canelón I, Sanchez-Cano C et al. Asymmetric transfer hydrogenation by synthetic catalysts in cancer cells. Nat. Chem. (Epub ahead of print) (2018) doi:10.1038/nchem.2918; https://warwick.ac.uk/newsandevents/pressreleases/cancer_targeted_with