Active substance from plant slows down aggressive eye cancer

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An active substance that has been known for 30 years could unexpectedly turn into a ray of hope against eye tumours.

The results have been published in the journal Science Signaling.

The plant leaves of which contain the tested substance are anything but rare – during Christmas time you can find it in every well-assorted garden centre.

The coralberry decorates many German living rooms during the winter months.

At this time it forms bright red fruits, which make it a popular ornamental plant.

The plant, originally from Korea, is surprisingly resistant to insect attack and its’ leaves contain bacteria that produce a natural insecticide – a toxin with the cryptic name FR900359 (FR).

This toxin could soon become a star in a completely different field – as a potential drug against uveal melanoma, the most common and aggressive variant of eye cancer.

FR has been the focus of pharmaceutical research for some time now and was isolated for the first time 30 years ago by Japanese researchers.

“The substance inhibits an important group of molecules in the cells, the Gq proteins,” explained Prof Evi Kostenis from the Institute of Pharmaceutical Biology at the University of Bonn.

Gq proteins have a similar function in the cell as a city’s emergency control centre.

When the control centre receives a call, it informs the police, ambulance and fire brigade as required.

Gq proteins, on the other hand, can be activated by certain control signals.

In their activated form, they switch different metabolic pathways on or off.

However, the cell should not permanently change its behaviour.

The Gq proteins, therefore, inactivate themselves after a short time.

In uveal melanoma, however, a tiny mutation prevents two important Gq proteins from returning to their inactive state.

They thus remain permanently active – this is as if the control centre were constantly sending emergency vehicles to the source of the fire, even though the fire has been extinguished for days.

Due to this malfunction, cells harbouring this mutation begin to divide uncontrollably.

“FR can stop this division activity,” said Kostenis. “That’s something no one would have expected.”

It has been known for some time that FR can prevent the activation of Gq proteins.

The substance “clings” to the proteins and ensures that they remain in their inactive form.

The common understanding was that FR ignores any Gq proteins that have already been activated.

“Therefore, it seemed impossible for the substance to be effective in mutated and thus permanently active Gq proteins,” emphasised Dr Evelyn Gaffal.

“We also used FR in our experiments and were surprised to find that it suppresses the proliferation of cancer cells,” Dr Gaffal explained.

Scientists now also know why this is so – the mutated Gq proteins also seem to occasionally revert into their inactive form.

As soon as this happens, FR intervenes and gets a firm grip on the molecule.

As a result, over time, more and more Gq proteins are successively withdrawn from their activated state for good.

FR has already proven its effectiveness in cell cultures and in experiments with mice suffering from cancer.

But there are still a few hurdles to overcome before application in humans becomes feasible.

Above all, the substance must reach the tumour cells precisely, without hitting other tissues.

“Gq proteins assume vital functions practically everywhere in the body,” mentioned Prof Kostenis. “If we want FR to kill only the tumour cells, we have to get the drug right there. However, this is a challenge that many other chemotherapies also have to deal with.”


Source: University of Bonn

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The ONA Editor curates oncology news, views and reviews from Australia and around the world for our readers. In aggregated content, original sources will be acknowledged in the article footer.

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