The University of Johannesburg (UJ) said on Tuesday that "a new family of very promising silver-based anti-cancer drugs" has been discovered by researchers.

The university said the most promising silver thiocyanate phosphine complex among those researched‚ known as UJ3‚ has been successfully tested in rats and on human cancer cells in the laboratory.

In research published in BioMetals‚ the university states that UJ3 is shown to be as effective against human esophageal cancer cells as a widely used chemotherapy drug in use today. Esophageal cancer cells are known to become resistant to current forms of chemotherapy.

"The UJ3 complex is as effective as the industry-standard drug cisplatin in killing cancer cells in laboratory tests done on human breast cancer and melanoma‚ a very dangerous form of skin cancer‚" Prof Marianne Cronjé‚ head of the department of biochemistry at UJ‚ said in a statement. "However‚ UJ3 requires a 10-times lower dose to kill cancer cells. It also focuses more narrowly on cancer cells‚ so that far fewer healthy cells are killed."

Apart from needing a much lower dose than the industry standard‚ UJ3 is also much less toxic‚ the statement said. "In rat studies‚ we see that up to 3g of UJ3 can be tolerated per 1kg of bodyweight. This makes UJ3 and other silver phosphine complexes we have tested about as toxic as Vitamin C‚" commented Prof Reinout Meijboom‚ head of the department of chemistry at UJ.

If UJ3 becomes a chemotherapy drug in future‚ the university researchers believe the lower dose required‚ lower toxicity and greater focus on cancer cells will mean fewer side effects from cancer treatment.

How it works

UJ3 appears to target the mitochondria‚ resulting in programmed cell death to kill cancer cells — a process called apoptosis. When a cancer cell dies by apoptosis‚ the result is a neat and tidy process where the dead cell’s remains are "recycled"‚ not contaminating healthy cells around them‚ and not inducing inflammation.

Certain existing chemotherapy 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‚ than healthy cells do. In this way they create cancerous tumours. To do this‚ they need far more energy than healthy cells do.

UJ3 targets this need for energy‚ by shutting down the "powerhouses" of a cancer cell‚ the mitochondria. The complex then causes the release of the "executioner" protein‚ an enzyme called caspase-3‚ which goes to work to dismantle the cell’s command centre and structural supports‚ cutting it up for recycling in the last stages of apoptosis.

Unusual compound

The university said the UJ3 complex and others in the family are based on silver. "This makes the starter materials for synthesising the complex far more economical than a number of industry-standard chemotherapy drugs based on platinum."

Meijboom said: "These complexes can be synthesised with standard laboratory equipment‚ which shows good potential for large-scale manufacture. The family of silver thiocyanate phosphine compounds is very large. We were very fortunate to test UJ3‚ with its unusually ‘flat’ chemical structure‚ early on in our exploration of this chemical family for cancer treatment."

Research on UJ3 and other silver thiocyanate phosphine complexes at the university is ongoing. The research was funded by the Technology Transfer Office of UJ‚ the National Research Foundation of SA‚ and the Technology Innovation Agency of SA.