Why frogs could be our saviour against cancer

New research is identifying chemicals in frogs that could lead to treatments for cancer and other health problems.

Frogs can be deadly. Take the Golden Dart Frog (Phyllobates terribilis) from South America, for example. One of these frogs is said to be able to produce enough poison to kill 10 humans or 20,000 mice.

But there are other types of deadly frogs. Thankfully, they're not deadly to humans, but they are ferocious against cancer cells and bacteria.

Researchers in the University of Adelaide's School of Chemistry and Physics have been studying the chemical properties of frogs for more than a decade. Professor John Bowie and colleagues, including Associate Professor Mike Tyler (Earth & Environmental Sciences) and Dr Ian Musgrave (Pharmacology), have been looking at "bioactive peptides" from frogs. Peptides are short molecules made out of amino acids that have the ability to interact with other cells and molecules.

Different peptides exist in many animals and insects, even in humans, helping with immune responses or, in the case of neuropeptides, the contraction and relaxation of muscles, among many other things.

Understanding what these peptides are, how and why they work and what they look like is essential to research efforts aimed at assisting the human race to fight a range of illnesses including cancer, heart disease and stroke.

Chemistry PhD student Tara Pukala has recently completed her research identifying the structure of particular peptides in frogs that could be used as anti-bacterial and anti-cancer agents. Supervised by Professor Bowie (Chemistry) and Dr Grant Booker (Biochemistry), Tara has spent the past few years detailing two main types of peptides from two groups of Australian frog species.

"Peptides and proteins are the basic building blocks and the machinery of the cells. They're used as messenger molecules and structural molecules. The frog uses them as a defence, so the peptides will attack and destroy bacteria and other foreign cells," Tara says.

"The way they do this is that they bind to the membrane of a cell and burst it open, degrading the cell. In the same way that they bind to bacterial cells they also bind to cancer cells and burst them open.

"They're not always specific as to which bacteria or cancer cells they attack."

Tests conducted at the Cancer Institute in Washington, United States, show that the peptides from Australian frogs being studied at Adelaide are active against 60 standard cancer cell lines.

"It's quite broad. There could be the potential to develop these frog peptides as pharmaceuticals that will act as anti-bacterial or anti-cancer treatments, and that's why being a part of this overall field of research is interesting," Tara says.

The peptides she has studied come from two groups of frog species: Litoria (best known because of the Australian green tree frog), and Crinia. Litoria frogs produce the Caerin group of peptides, while Crinia frogs produce neuropeptides known as Riparins.

The Caerin peptides are those that attack the membranes of cancer cells and bacteria, while the Riparins are important for enhancing immune responses and in muscle control. Theoretically, it might be possible to use Riparins to control blood pressure or as a muscle relaxant.

The importance of Tara's work is in the structure of the peptides and the way that relates to how they work.

"The idea is that we can tell the difference between peptides by relating their structure to their activity," she says. "If they are going to form, say, a helical structure, then they are more likely to be anti-bacterial; a small helical structure will indicate a `cancer breaker'. On the other hand, a peptide that has a more random form may have a completely different activity--it's likely to be active against an enzyme than against bacteria."

A single frog can have about 10 different peptides, which makes the research fairly time consuming.

"It takes about a month or so to work out the 10 peptides--that's not such a big deal. But then to actually work out the three-dimensional structure of a single peptide is quite a bit of work, maybe six months at a time. It's like a big jigsaw puzzle--you need to put it all together, to see how the atoms sit together in place. So that's a bit of work.

"We use a lot of hi-tech equipment, partly because you're looking at things on such a small scale. We also don't have access to large amounts of material, so we need to use very sensitive instruments and techniques," Tara says.

"We use techniques like mass spectrometry to give us ways of working out the sequence of the peptide, and nuclear magnetic resonance spectroscopy to determine their overall three-dimensional structure."

With Tara's research in Adelaide coming to an end, she's now been awarded a postdoctoral position at Cambridge University working in mass spectrometry with Professor Carol Robinson.

While she's obviously looking forward to the opportunity, Tara already has her sights set on returning to Australia.

"I think the opportunities for research here are as good as anywhere else, and this is my home, so I'd like to come back," she says. "I see going overseas as a chance to get some experience and to challenge myself a bit, to get out of my comfort zone.

But I'll come back after a few years."

Meanwhile, research into frog peptides and other related areas is ongoing at the University of Adelaide, with Professor Bowie and his colleagues continuing to win research funding and attracting national and international collaborators. ■

Story David Ellis

No frogs are harmed during this research, which is why many owners of frogs are happy for their pets to be participants.

So that researchers can get enough peptides to work with, a mild electrical probe is run over the frog's back. "It's like touching a nine-volt battery to your tongue," Tara says.

The electrical stimulus produces a response from the frog, which secretes peptides from its glands in an effort to protect itself.

What's in a name?

There's no doubt that Dr Mike Tyler, Visiting Research Fellow in the School of Earth and Environmental Sciences, has made a unique contribution to the study of frogs.

But what's even more unique is the fact that his name has been permanently linked to a number of frogs in Australia and around the world. That's because research colleagues have named frogs they've discovered after Dr Tyler.

Seven frogs in total bear Dr Tyler's name. They are:

Litoria tyleri
Australia

Litoria michaeltyleri
New Guinea

Tylerana
New Guinea

Tylerdella
Australia

Copiula tyleri
New Guinea

Nyctimystes tyleri
New Guinea

Uperoleia tyleri
Australia

In addition to frogs, colleagues have also named a caddis fly, a fairy shrimp and a frog parasite after him.

Dr Tyler has responded in kind, naming several frogs he's discovered after colleagues in Australia and across the globe.