Wallflowers could lead to new drugs to treat cancer, heart disease: Study

Wallflower can be used as an excellent model for discovering new plant-derived chemicals called cardenolides that could be used to treat heart disease and cancer, suggests recent research.

Cardenolides have long been used to treat heart disease, and have shown potential as cancer therapies. But the compounds are very toxic, making it difficult for doctors to prescribe a dose that works without harming the patient.

The study published online in eLife, a multi-institution team led by Boyce Thompson Institute faculty member Georg Jander and Tobias Zust, a research associate at the University of Bern's Institute of Plant Sciences, showed that Erysimum cheiranthoides (wormseed wallflower) could be used as a model species.

"I was looking for the best plant to study this pathway and settled on wormseed wallflower," Jander said, who is also an adjunct professor at Cornell University's School of Integrative Plant Science.

The species is a great model for genetic studies because it has a short life cycle and is readily inbred, he said.

"We need a plant that reproduces and gives us seeds quickly, which E.cheiranthoides does in about 10 weeks," he added.

In this study, the team assembled the complete genome of the wormseed wallflower and sequenced more than 9,000 expressed genes from E.cheiranthoides and 47 other Erysimum species.

The results provide a foundation for identifying the genes that encode enzymes involved in the biosynthesis of cardenolides. For example, the team discovered potential pathways by which Erysimum species modify a basic precursor cardenolide, digitoxigenin, into eight more structurally complex molecules.

To further enable the use of E.cheiranthoides as a model, the genome was assembled with long-read data and Hi-C scaffolding, a method that can provide a more contiguous genome than previous approaches, said Susan Strickler. Strickler is the director of the BTI Computational Biology Center (BCBC) and senior research associate at BTI.

"A high-quality reference genome makes it easier for us to find genes of interest and their locations, in this case, genes for the biosynthesis of cardenolides," she said.

The team is now conducting mutagenesis studies in E.cheiranthoides to allow them to find the entire cardenolide biosynthetic pathway.

"Ultimately the genes underlying the biosynthetic pathways could be inserted into bacteria or yeast, which would be used to manufacture heart and cancer medicines that are safer than what is currently available," said Jander.

The team's findings suggest the genus originally produced glucosinolates as an ancestral defense, then acquired the ability to produce cardenolides as recently as 2 to 4 million years ago as part of an "arms race" between plants and insects.

This second line of defense gives Erysimum an advantage against its insect enemies because none has yet developed resistance to cardenolides.

The first author of the study, Zust said it was also surprising to find no apparent cost to Erysimum, in terms of growth, reproduction or general fitness, in maintaining both defensive systems.

"In all but one of the species we studied, both systems are expressed and we don't see any apparent tradeoffs," Zust added.

However, he theorized that the cost of maintaining dual defenses might be reflected in the rarity of Erysimum species: they are not widely distributed and grow in small patches only in niche environments - such as cracks and roadsides - not colonized by other plant species.

( With inputs from ANI )