New Silver-based Chemotherapy Drug Kills Cancer Cells

Silver-based anti-cancer drugs based on silver thiocyanate phosphine complex have been developed and tested in rats and in human cancer cells in the laboratory by recent research in South Africa. The most promising silver thiocyanate phosphine complex among these, called UJ3 for short, has been successfully tested in rats and in human cancer cells in the laboratory.

The research team shows that UJ3 is more effective against human esophageal cancer cells than chemotherapy drugs currently in use today.

"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, as well. 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,” ," says Professor Marianne Cronjé, Head of the Department of Biochemistry at the University of Johannesburg.

Chemotherapy with less side-effects
The new drug, UJ3, is much less toxic than current chemotherapy drugs and requires a much lower dose.

According to Professor Reinout Meijboom, Head of the Department of Chemistry at the University of Johannesburg, rat studies have shown up to 3 grams of UJ3 can be tolerated per 1 kilogram of bodyweight which makes it as toxic as Vitamin C.

If UJ3 becomes a chemotherapy drug in future, there will be lower dosage, lesser toxicity, and more impact on cancer cells. Thus, this will reduce treatment side-effects.

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Hope for side-effect free cancer treatment
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.

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Cancer cells grow much bigger and faster, and make copies of themselves much faster, than healthy cells do. In this way they create cancerous tumors. 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 center and structural supports, cutting it up for recycling in the last stages of apoptosis.

See microscope images of human esophageal cancer cells treated with the UJ3 complex.

Unusual compounds for novel cancer treatment
Since UJ3 complex and the others in the family are based on silver, the starter materials for synthesizing the complex are far more economical than a number of industry-standard chemotherapy drugs based on platinum.

"These complexes can be synthesized 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 is unusually ’flat’ chemical structure, early on in our exploration of this chemical family for cancer treatment," says Prof Meijboom.

References:

1. Zelinda Engelbrecht, Reinout Meijboom, Marianne J. Cronje. The ability of silver(I) thiocyanate 4-methoxyphenyl phosphine to induce apoptotic cell death in esophageal cancer cells is correlated to mitochondrial perturbations, BioMetals http://dx.doi.org/10.1007/s10534-017-0051-9

Source-Medindia