New silver (I) complexes offer a silver lining for the future of cancer treatment
A prolific research collaboration between Prof Reinout Meijboom who is also the head of the Chemistry Department, Prof Marianne Cronje and Dr Zelinda Engelbrecht from the Biochemistry Department has reported the anti-cancer activity a silver(I) thiocyanate 4-methoxyphenyl phosphine complex (also known as UJ3) in the international journal BioMetals. This work follows a 10-year long research project on the synthesis and biological evaluation of silver phosphine complexes for their anti-cancer activities.
Laboratory tests of complex UJ3 revealed its excellent anti-cancer activities against malignant oesophageal cancer cell lines. Effective at 3.5 µM concentrations, UJ3 was found to be potent at concentrations 10 times lower than the current cancer treatment drug Cisplatin. The mode of action of UJ3 is proposed to be through apoptosis which is programmed cell death that does not cause inflammation or harm to surrounding cells. Investigations from the study indicate that the complex targets the mitochondria whereupon normal cellular functioning is interrupted resulting in a cellular production of low ATP, altered ROS activity, mitochondrial membrane depolarization, cytochrome c release and caspase-9 cleavage. Ultimately, all these irregular cytoplasmic events lead to the observed apoptosis.
In vitro toxicity studies against non-malignant human skin (HDFa) and kidney cell lines (HEK293) were found to be low, thus, indicating its specificity towards cancerous cells. This will result in reduced chemotherapeutic side effects that are often associated with cancer treatment drugs. Furthermore, the complex was found to be non-toxic in lab rats at doses of over 1300 g per kg of rats. Other advantages associated with UJ3 include the low cost and effortless lab synthesis of the complex and its simple derivatization into several structurally related analogues. Overall, these properties set up the complex as a much needed potential future drug for cancer treatment. Cancer research in this group in still continuing and more exciting results will be revealed in the near future. Congratulations to Prof Meijboom and his team!
This research project has been financially supported by the University of Johannesburg and the National Research Foundation of South Africa.
For more info on the conducted research please click on the links below:
BioMetals research article: