The sea cucumber has been found to naturally produce a sugary compound that inhibits an enzyme instrumental in facilitating cancer growth, according to a new study. The next step is to find a method for producing the marine-derived anticancer compound in large quantities.
Used for centuries in traditional medicines, particularly in Asia, sea cucumbers are rich in bioactive compounds with potential medicinal benefits. In 2023, we reported that the marine creatures contained key ingredients that could delay the onset of type 2 diabetes.
Now, new research, led by the University of Mississippi (UM), has found that another of the sea cucumber’s unique natural compounds blocks an enzyme that’s instrumental in facilitating cancer growth.
“Marine life produces compounds with unique structures that are often rare or not found in terrestrial vertebrates,” said the study’s lead author, Marwa Farrag, a PhD candidate in UM’s Department of Biomolecular Science and an assistant lecturer in the Faculty of Pharmacy at Assiut University, Egypt. “And so, the sugar compounds in sea cucumbers are unique. They aren’t commonly seen in other organisms. That’s why they’re worth studying.”
The surface of nearly all human cells is covered in glycans, a dense network of hair-like projections of complex carbohydrate molecules that are crucial to cell-cell communication and immune responses. Modified or abnormally expressed glycans have been linked to cancer growth and spread, or metastasis. An enzyme called heparan-6-O-endosulfatase 2, otherwise known as Sulf-2, has been found to modify glycans and, for that reason, has been implicated in cancer progression.
“The cells in our body are essentially covered in ‘forests’ of glycans,” said Vitor Pomin, corresponding author and an Associate Professor of Pharmacognosy at UM, which is the scientific study of medicinal drugs obtained from natural sources such as plants, animals, and minerals. “And enzymes change the function of this forest – essentially prunes the leaves of that forest. If we can inhibit that enzyme, theoretically, we are fighting against the spread of cancer.”
Previous studies have also investigated the pharmacological activities of a polysaccharide found in the sea cucumber species Holothuria floridana called fucosylated chondroitin sulfate (HfFucCS). Polysaccharides are complex carbohydrates made of long chains of simple sugar molecules, or monosaccharides. In the present study, the researchers examined the interaction between HfFucCS and the Sulf-2 enzyme and, using computer modeling and lab testing, confirmed that HfFucCS inhibited Sulf-2.
“We were able to compare what we generated experimentally with what the simulation predicted, and they were consistent,” said co-author Robert Doerksen, Professor of Medicinal Chemistry and Research Professor in the Research Institute of Pharmaceutical Sciences at UM. “That gives us more confidence in the results.”
Importantly, the researchers found that HfFucCS didn’t interfere with blood clotting, like some Sulf-2-targeting drugs do. Normally, Sulf-2 has a pro-clotting effect, making clot formation in the body slightly more likely. When Sulf-2 is blocked, there’s usually an increase in anticoagulant, or anti-clotting, activity.
“As you can imagine, if you are treating a patient with a molecule that inhibits blood coagulation, then one of the adverse effects that can be pretty devastating is uncontrolled bleeding,” said Joshua Sharp, UM Associate Professor of Pharmacology and another of the study’s co-authors. “So, it’s very promising that this particular molecule that we’re working on doesn’t have that effect.”
There are also benefits to using a natural source such as the sea cucumber, the researchers said.
“Some of these drugs we have been using for 100 years, but we’re still isolating them from pigs because chemically synthesizing it would be very, very difficult and expensive,” Sharp said. “That’s why a natural source is really a preferred way to get at these carbohydrate-based drugs.”
“It’s more beneficial and a cleaner resource,” added Pomin. “The marine environment has many advantages compared to more traditional resources.”
However, there is not an unlimited supply of the marine creatures, which are a popular food source throughout Asia. This means the researchers will need to devise a method for chemically producing the all-important sugar compound, HfFucCS.
“One of the problems in developing this as a drug would be the low yield, because you can’t get tons and tons of sea cucumbers,” Pomin said. “So, we have to have a chemical route, and when we’ve developed that, we can begin applying this [compound] to animal models.”
The study was published in the journal Glycobiology.
Source: University of Mississippi
