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New Compound Seen Killing Cancer Cells from Inside

Date: 
Monday, February 13, 2017

Cancer cells can be targeted and destroyed from the inside using a new organo-metal compound, discovered by the University of Warwick and imaged using the powerful X-rays of the ESRF.

Current statistics indicate that one in every two people will develop some kind of cancer during their life time. Chemotherapy is regularly used to treat this disease, and more than half of all cancer chemotherapy treatments currently use platinum compounds, which were introduced nearly 40 years ago. Despite their success, resistance to platinum is now a clinical problem, as is the need to reduce side-effects (from renal failure to neurotoxicity, ototoxicity, nausea and vomiting) and extend treatment to a wider range of cancers. Therefore, there is a real need to explore the benefits that other precious metals could bring to find more effective ways of defeating cancerous cells.

Ovaran cancer cells under nano-focus (2 micron scale), showing FY26, zinc and calcium. Credit: University of Warwick

Back in 2008, Peter Sadler and his team in the University of Warwick (UK) showed that Osmium, with its special chemical properties, offers a new promise solution in treating several different types of cancers, including ovarian and colon cancers. The metal also has another advantage in that it is a much cheaper alternative to platinum

In this publication, thanks to ESRF synchrotron X-Ray fluorescence nanoprobe, Peter Sadler and his group in the Department of Chemistry have demonstrated that Organo-Osmium FY26 – which was first discovered at Warwick – kills cancer cells in ovarian cancer (the 8th most common cause of cancer death worldwide) by locating and attacking their weakest part. This is the first time that an Osmium-based compound – which is fifty times more active than the current cancer drug cisplatin - has been used to target the disease.

Using one of the world most brilliant synchrotron sources, the ESRF, and its new nano-imaging ID16A beamline, researchers analysed the effects of Organo-Osmium FY26 in ovarian cancer cells – detecting emissions of X-ray fluorescent light to track the activity of the compound inside the cells. Looking at sections of cancer cells under X-ray nano-focus, they could see an unprecedented level of minute detail. Organelles like mitochondria, which are the ‘powerhouses’ of cells and generate their energy, were detectable. In cancer cells, there are errors and mutations in the DNA of mitochondria, making them very weak and susceptible to attack.

The osmium compound was found to have positioned itself in the mitochondria - attacking and destroying the vital functions of cancer cells from within, at their weakest point. Organo-Osmium FY26 has been shown to be more selective between normal cells and cancer cells than cisplatin – and has a greater effect on cancer cells than healthy ones.

Although this research was conducted on ovarian cancer cells, the ground-breaking results are applicable to a wider range of cancers. Sadler comments that this research could lead to new cancer treatments: “Cancer drugs with new mechanisms of actions which can combat resistance and have fewer side-effects are urgently needed. The advanced nano-focussed X-ray beam at the ESRF has not only allowed us to locate the site of action of our novel Organo-Osmium FY26 candidate drug in cancer cells at unprecedented resolution, but also study the movement of natural metals such as zinc and calcium in cells. Such studies open up totally new approaches to drug discovery and treatment”.

Professor Sadler’s group, including research fellows Carlos Sanchez and Isolda Romero Canelon, gained their results with Peter Cloetens, Yang Yang and Sylvain Bohic at the ESRF. Peter Cloetens comments on how the ID16A beamline allows experiments with real-life doses: "These kinds of experiments are normally performed using bigger doses than what would be done in real life or on a coarse scale that does not provide a clear picture of the processes that take place. On the new nano-imaging ID16A beamline, however, by combining a very tight focus and high flux, we could get a real picture of where the drug goes in a single cell using real-life pharmacological doses."

Sánchez-Cano C., et al, Chemistry, 2017.

The research is funded by grants from Cancer Research UK & Engineering and Physical Sciences Research Council, The Wellcome Trust, and the European Research Council.

 

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