Scientists unlock nature’s secret to a cancer-fighting molecule

Mitraphylline is part of a small family of plant-derived molecules known as spirooxindole alkaloids. These compounds feature unique, “twisted” ring-like chemical structures and are recognized for their strong biological effects, including anti-tumor and anti-inflammatory activity.

Until recently, researchers did not understand the precise molecular process plants use to form spirooxindoles. That changed in 2023 when Dr. Thu-Thuy Dang and her team in the Irving K. Barber Faculty of Science identified the first plant enzyme capable of twisting a molecule into the distinctive spiro shape.

Building on that milestone, doctoral student Tuan-Anh Nguyen led the next phase of research and uncovered two enzymes that work together: one determines the molecule’s 3D arrangement, and the other completes the final twist that forms mitraphylline.

"This is similar to finding the missing links in an assembly line," says Dr. Dang, UBC Okanagan Principal's Research Chair in Natural Products Biotechnology. "It answers a long-standing question about how nature builds these complex molecules and gives us a new way to replicate that process."

Because natural compounds often exist in only tiny quantities, they can be difficult and expensive to produce in the laboratory. Mitraphylline is one such compound, found in trace amounts in tropical trees like Mitragyna (kratom) and Uncaria (cat’s claw), both members of the coffee family.

By identifying the enzymes responsible for assembling and shaping mitraphylline, the researchers have established a framework for producing this and related compounds more efficiently and sustainably.

"With this discovery, we have a green chemistry approach to accessing compounds with enormous pharmaceutical value," says Nguyen. "This is a result of UBC Okanagan's research environment, where students and faculty work closely to solve problems with global reach."

"Being part of the team that uncovered the enzymes behind spirooxindole compounds has been amazing," Nguyen adds. "UBC Okanagan's mentorship and support made this possible, and I'm excited to keep growing as a researcher here in Canada."

The project is the result of collaboration between Dr. Dang's lab at UBC Okanagan and Dr. Satya Nadakuduti's team at the University of Florida.

The work was supported by Canada's Natural Sciences and Engineering Research Council's Alliance International Collaboration program, the Canada Foundation for Innovation, and the Michael Smith Health Research BC Scholar Program. Support also came from the United States Department of Agriculture's National Institute of Food and Agriculture.

"We are proud of this discovery coming from UBC Okanagan. Plants are fantastic natural chemists," she says. "Our next steps will focus on adapting their molecular tools to create a wider range of therapeutic compounds."