In Pakistan, there grows a plant that goes by the scientific name Withania coagulans. Local shamans have used it for centuries to cure a long list of ailments, from headaches and nausea to insomnia and impotence. Farmers use it to help coagulate cheese. The plant’s compact kernels, known commercially as Indian rennet, are sold as an herbal remedy to help control diabetes.
It is, in other words, a particularly useful medicinal plant.
But its greatest use may be yet to come. In a series of preliminary studies, secondary compounds in the plant called withanolides have shown promise in slowing the growth and mobility of prostate cancer cells, offering a potential new treatment in the fight against the deadly disease.
“We finally understand a bit more what types of compounds might be active against cancer,” explains Ken Keefover-Ring, an assistant professor in the departments of Botany and Geography. “So now there’s this big search, taking a lot of these medicinal plants containing these compounds and screening them against standard sets of cancer cells to see the level of activity against them. It doesn’t mean it’s going to be the next cancer drug. But sometimes it is.”
In other words, plants are having a big moment in the world of cancer research, and that means botanists are, too.
As is often the case with the development of medical treatments, it’s a long path from promise to reality, and there are many variables at play. Last year, Keefover-Ring, a chemical ecologist who studies how plant secondary compounds help mediate the interactions between plants and other organisms, helped to sketch in an important part of that still-developing picture. He partnered with Dr. Samiya Rehman, a recent graduate student from Pakistan, to study the question of whether W. coagulans plants grown in drier climates have increased levels of withanolides. Their findings were published in the Journal of Applied Biochemistry and Biotechnology.
Rehman sought out Keefover-Ring because of his expertise with and access to equipment that could conduct a process called ultra-high-pressure liquid chromatography, or UHPLC. He ran solutions of extracts from plants taken from 11 sites in Pakistan through a small metal column filed with silica that separates organic compounds according to their polarity.
“At the end of the day, you want to know, ‘How much active compound per gram of extracted material do you have here?” says Keefover-Ring.
The UHPLC process showed that extracts from plants grown in two of the 11 areas—both areas with significantly drier climate conditions—had up to 17 times the amount of withanolides as compared to plants grown in areas with greater rainfall. Guided by these results, Rehman then tested plant extracts from two populations with the highest amounts of withanolides against prostate cancer cell lines.
“Scanty rainfall, extreme temperature variation range, and high altitudes can play a role to make a plant produce more secondary metabolites and have more anticancer activity as compared to the plants growing in favorable environmental conditions,” says Rehman. “Potent anticancer activity was directly proportional to stressed environmental conditions.”
For Keefover-Ring, the wetter-is-less, drier-is-more finding points up the critical importance of the same thing that’s valued by realtors and major-league baseball pitchers: Location, location, location.
“A species’ chemistry is not the same everywhere,” Keefover-Ring explains. “Even within a species, there can be huge differences.”
To illustrate his point, Keefover-Ring points to thyme, the common kitchen herb. In France, the location and environment in which thyme is grown and its evolutionary history with different herbivores have a profound effect on its scent and taste. In some places, thyme tastes sweeter; in others, it carries an oregano scent. These different essential oil types exist in the same species, due to relatively small genetic differences.
“We tend to think, ‘Okay, thyme, that’s just what it smells like,’” says Keefover-Ring. “Well, that’s because we’ve chosen that chemotype, we propagate it in huge amounts, and that’s the only one we use.”
The same thing could now be true of Withania coagulans. Keefover-Ring and Rehman’s project is a gateway study, a sort of key proof-of-concept exercise that opens pathways for other researchers to explore. Next steps are likely to involve further exploration of the individual compounds found in the UHPLC analysis. Back in Pakistan, Rehman’s hoping to collaborate with hospitals to use the study’s findings to help create anticancer drugs from the withanolides.
“Pakistan is rich in natural resources,” she says. “Medicinal plants are one of those resources.”