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Suppressive drug reactions are more frequent than previously known

by Lindsay Jolivet Apr 22 / 14

Drugs suppress other drugs much more often than previously realized, according to a new study that tested the effect of different drug pairs on yeast growth.

Researchers have found the first example of drug compounds that simultaneously suppress each other. 
Photo: iStock

A collaboration of researchers including CIFAR Senior Fellow Frederick Roth (Samuel Lunenfeld Research Institute) tested pairs of 220 drugs on yeast, measuring their effects on growth. Used alone, all of the drugs tested had properties that would slow the growth of yeast. However, if a drug pair had a suppressive interaction, the yeast would grow more quickly instead. By choosing a large sample of different drugs and testing them all in combination, the researchers hoped to reveal how often suppression occurs.

“It’s happening really often,” says Roth, who is also the associate director of the program in Genetic Networks. About 17 per cent of the drug pairs showed a suppressive interaction. Some drugs showed a strong tendency to suppress other drugs, such as Bromopyruvate, a drug that medical researchers are testing for its potential to target and kill cancer cells. Others, such as Staurosporine, were susceptible to suppression by many of the other drugs in the study.

Roth says that while this research did not look at any medical effects in humans, the results suggest drugs have complex interactions on cells that we don’t fully understand.

“It’s not like drugs are magic bullets that just knock out one particular protein in a cell. They must be doing other things to explain how often this suppression is happening,” Roth says.

“If you wanted a drug to be specific, and only tinker with one part of a cell, this would give you pause.”

However, the study also discovered mutually suppressive reactions that could be useful for fighting antibiotic resistant strains of bacterial infection.

“There were actually no examples known previously of two drugs where each suppressed the other one,” Roth says.

The theory suggests that if a bacteria is resistant to one drug, using it in combination with another that both suppresses and is suppressed by it will fight the infection and prevent the bacteria from evolving even stronger resistance.

“The instant it’s resistant to one of the drugs, then all of a sudden it becomes more sensitive to the other one,” Roth says.

The concept remains a theory, but researchers now have examples to test for potential clinical uses.

The paper was published in the journal Chemistry & Biology.