mammalian-cell

Molecule of the Day: Cisplatin

Cisplatin [Pt(NH3)2Cl2] is an metal complex that is used as an antineoplastic agent (anti-cancer drug). It is one of the archetypal transition metal complexes, being well-known and having a long history.

Cisplatin was first synthesised in 1845 by Michele Peyrone, and was known as Peyrone’s salt. Its medicinal effects, however, were not known until the late 20th century, until it was discovered by chance.

In 1961, a physics professor by the name of Barnett Rosenberg at Michigan State University embarked on a project to investigate the effect of electromagnetic radiation on cells during mitotic division. To his surprise, the setup caused the E. coli to elongate instead (below right), without undergoing cell division.

Eventually, the suspicion fell on the platinum electrodes. They were indeed the culprit; in the presence of oxygen, it had produced cisplatin. The researchers then decided to test its effects on mammalian cells by injecting it into mice with tumours; the results are remarkable, as can be seen from the images below. The tumour of the mouse that was injected with cisplatin (2nd row) had completely regressed by day 8, while the mouse that was not (1st row) eventually died on day 21.

Currently, cisplatin is used to treat various, but not all, forms of cancer, such as breast, lung, testicular, and ovarian cancer. When administered, the Cl atoms are displaced by water molecules, which themselves are displaced by guanine or adenine molecules in DNA. Since two ligands can be displaced, cross-linking of DNA occurs, interfering with cellular division.

Interestingly, its geometric isomer, transplatin, does not have any medicinal effect; it is believed to be due to its rapid hydrolysis when administered, causing it to be unable to react with the DNA to cross-link it. Additionally, the inter-strand cross-linking it causes could be more easily repaired by DNA repair mechanisms than the intra-strand cross-linking that cisplatin causes.

Cisplatin is synthesised from potassium tetrachloroplatinate via multiple ligand exchange reactions with potassium iodide, followed by ammonia, silver nitrate, and potassium chloride respectively.

Visualizing the genome: First 3D structures of active DNA created

Scientists have determined the first 3D structures of intact mammalian genomes from individual cells, showing how the DNA from all the chromosomes intricately folds to fit together inside the cell nuclei.

Researchers from the University of Cambridge and the MRC Laboratory of Molecular Biology used a combination of imaging and up to 100,000 measurements of where different parts of the DNA are close to each other to examine the genome in a mouse embryonic stem cell. Stem cells are ‘master cells’, which can develop – or 'differentiate’ – into almost any type of cell within the body.

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Light opens up the larynx
Muscles engineered to be photosensitive could lead to treatments for paralysis.

Scientists have genetically engineered muscles to move in response to pulses of light.

The technique, demonstrated on vocal cords removed from mice, is reported on 2 June in Nature Communications1. Researchers say that it could probe how muscles function — and might eventually help to treat people who have a paralysis that interferes with speech and breathing.

The work relies on a method called optogenetics, which can make cells that usually respond to electrical signals also react to light. The approach alters mammalian cells by inserting a gene for a protein such as channelrhodopsin, which in its natural setting allows blue-green algae to swim towards or away from light.

Optogenetics was first used in 2005 to modify neurons2, and has since become a standard tool to study the brain and nervous system. Applications outside neuroscience, however, are less common.

The latest study is fascinating, says Julio Vergara, a physiologist at the University of California, Los Angeles, who studies how electrical signals cause muscles to contract. “It shows the potential use of this very powerful technique for very important medical problems,” he says.

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