Apart from the fiction related to werewolves, there has always been talk of finding a “silver bullet” to kill tumors, as declared by the researcher Domagk about a century ago. Perhaps time has proved him right.
A new family of very promising anticancer drugs based on silver has been discovered by researchers in South Africa. The most promising silver phosphine complex thiocyanate, called UJ3, was successfully tested in human laboratory rats and cancer cells. In the research published in the journal BioMetals, UJ3 proves effective against human esophageal cancer cells, as a widely used chemotherapy drug today. Esophageal cancer cells are known to become resistant to current forms of chemotherapy. “UJ3 is as effective as the standard cisplatin drug in breaking down cancer cells in laboratory tests, performed on human breast cancer and melanoma,” says Professor Marianne Cronjé, head of the Department of Biochemistry at the University of Johannesburg. “UJ3 requires a 10-fold lower dose to kill cancer cells”.
The drug also focuses more closely on cancer cells, so that far fewer healthy cells are killed. In addition to requiring a much lower dose of a standard chemotherapy, UJ3 is also much less toxic. In studies in rats, scientists have seen that up to 3 grams of UJ3 per 1 kilogram of body weight can be tolerated. This makes UJ3 and other silver phosphine complexes that have been as toxic as vitamin C. If UJ3 becomes a chemotherapy drug in the future, the lower dose required, less toxicity and a higher concentration on cancer cells will mean less side effects from cancer treatment. UJ3 appears to affect mitochondria, resulting in cell death programmed to kill cancer cells – a process called apoptosis. When a cancerous cell dies by apoptosis, the result is a clean and orderly process in which the remains of dead cells are “recycled”, not contaminating the healthy cells around them and not inducing inflammation.
Some existing chemotherapeutic drugs are designed to induce apoptosis, rather than “septic” cell death which is called necrosis, for this reason. Cancer cells grow much bigger and faster and make copies of themselves much faster, compared to healthy cells. In this way they create cancerous tumors. To do this, they need a lot more energy than healthy cells do. The UJ3 targets this need for energy, closing the “power stations” of a cancerous cell, the mitochondria. The complex then causes the release of the “hangman” protein, an enzyme called caspase-3, which dismantles the control center and the structural supports of the cell, cutting the main proteins for recycling in the last stages of apoptosis. The UJ3 complex and the other members of the family are based on silver. This makes the starting materials to synthesize the much cheaper complex of a number of platinum-based standard chemotherapeutic drugs.
These complexes can be synthesized with standard laboratory equipment, which shows good potential for large-scale production. Further research on UJ3 and other silver thiocyanate phosphine complexes at the University of Johannesburg is underway.
- edited by Dr. Gianfrancesco Cormaci, PhD, specialista in Biochimica Clinica.
Engelbrecht Z et al. Biometals 2018 Apr; 31(2):189-202.
Ahmad Khan R et al., J Inorg Biochem. 2014 Nov; 140:1-5.