A drug with multitasking potential

Recent studies have also indicated that aspirin can reduce the risk of stomach, oesophageal and colon cancers, when taken daily under medical supervision.

Dr Rabah Iratni , a lead physician and researcher, working in the laboratory at UAE University, Al Ain. Pawan Singh / The National
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It can seem surprising that drugs effective against one medical condition can sometimes be used to combat other, seemingly unrelated, illnesses.

For example, aspirin, one of the most widely available pharmaceuticals, as well as being used against headaches and other aches and pains, is also taken regularly by some people with cardiovascular disease, since its anti-clotting properties mean it can prevent heart attacks and strokes.

Recent studies have also indicated that it can reduce the risk of stomach, oesophageal and colon cancers, when taken daily under medical supervision.

The antibiotic salinomycin is less of a household name, but it too could be of value in dealing with a range of conditions. While currently used to prevent an intestinal disease in poultry called coccidiosis, research in Al Ain suggests it might also help to combat human cancer.

In a study published in the journal PLoS One, scientists at UAE University found salinomycin caused cell death in two lines of cultured lung cancer cells, known as LNM35 and A549.

The work involved maintaining the cancer cells in a medium, treating them with varying concentrations of salinomycin, and then watching to see if they lived or died.

A substance was added to the cells that caused them to be luminescent if they were metabolically active, so live cells gave off light, while dead cells didn’t.

And it was found that at high concentrations of salinomycin, up to 90 per cent of the cancer cells died.

It is thought salinomycin kills cells by activating types of protein called caspases, controlling a pathway causing cell death.

“It induces irreversible growth arrest [senescence] at low concentration and apoptotic cell death [death by a programmed sequence of events] at higher concentration,” said Dr Rabah Iratni, who carried out the research with five UAEU colleagues and a scientist at Nagoya University in Japan.

As reported in The National last year, Dr Iratni and his co-researchers have also helped to uncover the anti-cancer properties of the common herb marjoram.

Salinomycin didn’t just cause the cells to stop multiplying and to die; it also made them less able to migrate towards a chemical attractant.

This is significant because a key danger of cancer comes when cells travel to parts of the body away from the original cancer, forming new tumours, called metastases.

Salinomycin made the cells produce high levels of a protein, NAG-1, which appears to be involved in preventing cells from migrating.

The lung cancer work in Al Ain comes on top of findings from other scientists over the past five years that salinomycin is effective against cells from several types of cancer, including breast, ovarian and pancreatic cancers.

Indeed, an earlier study by Dr Iratni and fellow UAEU researchers found that salinomycin could block the growth of several types of breast cancer cell, and even cause those cells to die.

Still, a useful treatment is a way off. While described by Dr Iratni as “a promising novel therapeutic agent”, his team has thus far tested salinomycin only in cultured cells, not in whole animals, far less in people.

“Although [this] is the initial step to test the anti-cancer potential of new drugs, it does not really reproduce the natural environment of the tumour,” he said. “In vivo [in a living animal] experiments will provide precious information as to the type of cancer [against which] salinomycin would be best to use.”

So far, it shows promise for killing breast and lung tumours, as well as preventing metastasis.

Dr Sam Godfrey, a science information manager at the charity Cancer Research UK, said caution should additionally be sounded because the results also did not show whether salinomycin harmed healthy cells as well as cancer cells.

“So it’s impossible to say whether this drug could be used for selectively targeting tumours,” he said.

“Much more research is needed before we will know whether salinomycin will be any use as a safe and effective cancer treatment in the future.”

Not all the signs are promising, however.

Single-drug treatments rarely work very well; the best treatments are often combination therapies of a cocktail of substances. So scientists often hope their drugs will show positive interactions with others – showing promise as a useful part of a combination therapy.

The Al Ain scientists found that salinomycin’s anticancer action was not enhanced when it was used alongside an established lung cancer drug, cisplatin. The combination tests were more promising in the breast cancer cells, and Dr Iratni and his team are now running further tests to see what other anti-cancer active ingredients the antibiotic interacts well with.

The UAEU team are not the only ones looking as salinomycin. A German group, based at Ludwig Maximilian University of Munich, recently released findings that suggest salinomycin could help to combat cancers actually within whole organisms.

They found it “significantly reduced the metastatic tumour burden” in mice. It was, they said, the first piece of evidence salinomycin could prevent the formation of metastases in whole animals, “strengthening its role as a promising anti-cancer therapeutic”.

Dr Andreas Roidl, an author of the study, called it “a promising new anti-cancer drug”, partly because it targeted certain types of cancer cells other drugs were less effective against.

He too cautioned that there was still “a long way to go” to a real treatment. In particular, a lot of work is needed before the drug could be used, for example, in targeted therapies that ensure only cancer cells are destroyed and salinomycin’s “severe side effects” are eliminated.

For that, the German group is looking at using nanoparticles to deliver the drug in this targeted way.

Meanwhile, Dr Iratni and his colleagues are carrying out in vivo studies that could offer a better indication of the drug’s potential in the real world.

“We are ... testing the anticancer activity of salinomycin in vivo using chick embryo animal model,” he said.

Still, even if studies with animals go well, Dr Iratni believes clinical trials could be a decade off. There are many more hurdles to overcome before this antibiotic finds a place in the oncologists’ armoury.