Scientists have discovered two proteins secreted from the skin of frogs that could help treat cancer and other diseases by disrupting the growth of blood vessels: one switches the process of "angiogenesis" on, and the other switches it off. The researchers say the discovery has the potential to transform cancer from a terminal illness to a chronic condition.

The award-winning discovery is the work of Professor Chris Shaw and colleagues at Queen's University Belfast, in Northern Ireland.

Shaw is Professor in Drug Discovery at Queen's School of Pharmacy, where he specializes in finding and classifying naturally occurring, biologically active agents, most notably those found in the venom of amphibians all over the world.

In this latest discovery, Shaw and colleagues identified two mini-proteins or "peptides" (typically shorter than proteins but made from similar building blocks, amino acids) secreted on the skin of the Waxy Monkey Frog and the Giant Firebellied Toad that have the potential to stimulate or switch off "angiogenesis", the process of growing new blood vessels.

The peptide they found in skin of the Waxy Monkey Frog can switch off angiogenesis and the peptide they found in the skin of the Giant Firebellied Toad does the opposite: it can switch on angiogenesis.

As a cancer tumor grows and needs more oxygen and nutrients, it gets to a point where it has to develop its own blood supply, or it can't grow any bigger. So the idea is that a peptide that switches off angiogenesis could be incorporated into cancer drugs so the tumors either starve or stop growing.

In a statement to the press, Shaw explained the potential of such a compound:

"Stopping the blood vessels from growing will make the tumour less likely to spread and may eventually kill it. This has the potential to transform cancer from a terminal illness into a chronic condition."

On the other hand, a peptide that can switch on angiogenesis is also useful. For instance, in diseases or conditions where blood vessels need to repair quickly, such as in helping wounds to heal, in organ transplants, diabetic ulcers, and where strokes or heart conditions have left blood vessels damaged.

Angiogenesis has been a prime target for new drugs for over four decades, said Shaw, who said the reason he and his team look to the natural world for such compounds is because despite billions of investment by scientists and drug companies, man-made drugs that can effectively target and control the growth of blood vessels have yet to appear.

"We are absolutely convinced that the natural world holds the solutions to many of our problems, we just need to pose the right questions to find them," said Shaw.

"It would be a great shame to have something in nature that is potentially the wonder drug to treat cancer and not aim to do everything in our power to make it work," he added.

Shaw's team members are very careful when they handle the frogs, so as not to harm them. They gently extract the secretions, and then release the frogs back into the wild.

Other studies have also shown that amphibians synthesize and secrete a range of chemicals with antimicrobial properties.

Earlier this year, scientists Ren Lai and colleagues from China reported in the Journal of Proteome Research that they found 79 different antimicrobial peptides, including 59 that were totally new to science, in the brains of two types of toad. Some of the peptides were so powerful they could cripple or kill strains of staph bacteria, E. coli, and some types of fungus that infect humans.

Sources: Queen's University Belfast, AlphaGalileo Foundation, American Chemical Society, via EurekAlert!.

: Catharine Paddock, PhD

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