DeAdly mushroom may help fight cancer
Compounds in death cap can be utilized to kill cancer cells, researchers say
A deadly fungus that took the life of a three-year-old boy in B.C. two years ago may yet yield a life-saving cure.
Among the unique compounds found in the death cap mushroom is one that can be used to kill some kinds of cancer cells.
The toxin α-amanitin, applied to pancreatic tumours, cured 60 per cent of mice with cancer in a 2012 study.
The death cap — Amanita phalloides — has a sinister history. A boy in Victoria died after eating a death cap while foraging for edible mushrooms with his family.
It is said to have been used to murder the Roman Emperor Claudius.
Experts say the death cap accounts for about 90 per cent of all fatal mushroom poisonings worldwide.
In North America, the resemblance between newly sprouted death caps and straw mushrooms has caused the deaths of dozens of Asian immigrants, particularly in California, according to UBC chemist David Perrin.
“This is the mushroom that gives all mushrooms a bad name,” he said.
“There is no known antidote.” Death cap may also be mistaken for the highly prized matsutake or pine mushroom that grows in B.C. Locally, the deadly fungus is confined mainly to the Oak Bay area under oak and chestnut trees, which it needs to survive.
Typically, people who ingest the death cap become violently ill for a short time, then feel better for up to 10 days, at which time they die of liver failure.
That’s the bad news. The good news is that Perrin’s lab has succeeded in synthesizing α-amanitin and the means to build better versions of it for medicinal uses.
By customizing the molecule, Perrin aims to make it less toxic to the liver, selectively toxic to cancer cells and create structures that will help it attach to homing antibodies that will deliver its deadly payload directly to cancer cells.
Researchers in Germany are in trials with an α-amanitin compound derived from wild mushrooms. But only tiny amounts of the toxin can be extracted from wild mushrooms and collecting them is dangerous.
Larger amounts of the compound will be needed as research progresses from petri-dish scale to medical trials, to say nothing of the amounts required for commercial sales.
“And even if you have enough of the natural toxin, you can’t really modify it,” said Perrin.
“Our goal is to build a derivative with specific toxicity and that’s not something you can do working with the natural compound.”
Some of α-amanitin’s precursor building blocks are so delicate they blow apart when exposed to air or light, which makes it tricky to complete all the steps required to synthesize the final molecule without ruining it.
“It requires a choreography of different reactions and each product along the way has to be compatible with each reaction, and the next and the next, plus it has to be high-yielding,” he said.
Perrin is excited by the success other groups are having with cancer treatments in animal models, particularly in pancreatic cancer cells.
“If it translates to humans, that’s huge,” he said. “Pancreatic cancer is uniformly a death sentence.”