Preventing the spread of Cancer with Copper Molecules
Published 2. March 2015, 10:13 h
Chemists at Bielefeld University have developed a
molecule containing copper that binds specifically with DNA and prevents the
spread of cancer. First results show that it kills the cancer cells more
quickly than cisplatin – a widely used anti-cancer drug that is frequently
administered in chemotherapy. When developing the anti-tumour agent, Professor
Dr. Thorsten Glaser and his team cooperated with biochemists and physicists.
The design of the new agent is basic research. ‘How and whether the copper
complex will actually be given to cancer patients is something that medical
research will have to determine in the years to come,’ says the chemist. ‘Much of the research on anti-cancer drugs concentrates on
variants of cisplatin. Our copper complex, in contrast, is a completely new
agent,’ says Prof. Dr. Thorsten Glaser.
Ever
since the end of the 1970s, doctors have been using cisplatin to treat cancer.
For lung cancer and testicular cancer, the drug promotes healing; however, it
does not work for all types of cancer. Cisplatin is also one of the anti-cancer
drugs that most frequently induce nausea, vomiting, and diarrhoea. ‘Therefore
we wanted to develop an alternative agent that would work differently, have
fewer side effects, and treat other types of cancer as well,’ says Thorsten
Glaser, Professor of Inorganic Chemistry at Bielefeld University. ‘In addition,
we wanted an agent that would treat cancers that have become immune to
cisplatin through its use in earlier treatments.’ Glaser and his team are using
methods from chemistry to produce new molecules that are not found in nature,
and to equip these with specific properties. Cisplatin attacks the DNA of
cancer cells. DNA is composed of nucleobases, phosphates, and sugar. Whereas
cisplatin binds with the nucleobases, the new molecule developed by the
researchers attacks the phosphate in the DNA. ‘We did this by integrating two
metal ions of copper in our molecule that preferentially bind with phosphates.’
As soon as the ions bind with the phosphate, the DNA of the cancer cell
changes. This disrupts the cellular processes, prevents the cell from
reproducing, and leads to the destruction of the pathological cell. ‘Just as a
key only works in one specific lock, our molecule only fits the phosphates and
blocks them,’ says Glaser. A bit like the end of a horseshoe, there are two
metal ions of copper protruding from the new molecule. The gap between the two
ends of the horseshoe corresponds exactly to that between the phosphates in the
DNA so that they can dock together and form a perfect fit. ‘Because two
phosphates bind simultaneously, the binding strength is greater. And that
increases the efficacy.’
The
new agent containing copper (above) ‘docks’ precisely with the DNA molecule
(below) of a cancer cell and stops it from growing. As a result, the cancer
cell dies.
Photo: Bielefeld University
The
scientists at Bielefeld University have developed a procedure for manufacturing
the new molecule. They have proved that their copper agent can bind with DNA
and change it. And they have studied whether and how well their agent prevents
the spread of the DNA and thereby of the cells. The replication of the genome
in cells proceeds in a similar way to a polymerase chain reaction (PCR). The
researchers have confirmed that the copper complex stops this chain reaction. Finally,
the scientists applied the agent to cancer cells. They administered the
substance to a cell culture with cancer cells. The result was that ‘the copper
complex is more effective than cisplatin,’ says Glaser. ‘The highest number of
cancer cells died at a concentration of 10 micromolar. With cisplatin, you need
20 micromolar.’
When carrying out the research on the new agent, Professor Glaser and his team cooperated with the research teams of Professor Dr. Dario Anselmetti (Biophysics and nanoscience) and Professor Dr. Gabriele Fischer von Mollard (Biochemistry) – both also at Bielefeld University. Dario Anselmetti’s colleagues used atomic force microscopy to produce the images confirming that the copper complex binds with the DNA. Gabriele Fischer von Mollard’s team tested how the cancer cell culture responded to the agent. The three research groups are cooperating within Collaborative Research Centre (CRC) 613 ‘Physics of Single-Molecule Processes and of Molecular Recognition in Organic Systems’.
When carrying out the research on the new agent, Professor Glaser and his team cooperated with the research teams of Professor Dr. Dario Anselmetti (Biophysics and nanoscience) and Professor Dr. Gabriele Fischer von Mollard (Biochemistry) – both also at Bielefeld University. Dario Anselmetti’s colleagues used atomic force microscopy to produce the images confirming that the copper complex binds with the DNA. Gabriele Fischer von Mollard’s team tested how the cancer cell culture responded to the agent. The three research groups are cooperating within Collaborative Research Centre (CRC) 613 ‘Physics of Single-Molecule Processes and of Molecular Recognition in Organic Systems’.
Original publication:
Thomas Jany, Alexander Moreth, Claudia Gruschka, Andy Sischka, Andre Spiering, Mareike Dieding, Ying Wang, Susan Haji Samo, Anja Stammler, Hartmut Bögge, Gabriele Fischer von Mollard, Dario Anselmetti, Thorsten Glaser: Rational Design of a Cytotoxic Dinuclear Cu2 Complex That Binds by Molecular Recognition at Two Neighboring Phosphates of the DNA Backbone. Inorganic Chemistry, http://dx.doi.org/10.1021/ic5028465, published on 4 February 2015.
Contact: Prof. Dr. Thorsten Glaser, Bielefeld University
Faculty of Chemistry, Telephone: 0521 106-6105
Email: thorsten.glaser@uni-bielefeld.de
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