Sea Cucumbers Could Hold Key to Stopping Cancer Spread

A sugar compound found in sea cucumbers can effectively block Sulf-2, an enzyme that plays a major role in cancer growth, according to a University of Mississippi-led study published in Glycobiology.

"Marine life produces compounds with unique structures that are often rare or not found in terrestrial vertebrates," said Marwa Farrag, a fourth-year doctoral candidate in the UM Department of BioMolecular Sciences.

"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."

Farrag, a native of Assiut, Egypt, and the study's lead author, worked with a team of researchers from Ole Miss and Georgetown University on the project.

Human cells, and those of most mammals, are covered in tiny, hairlike structures called glycans that help with cell communication, immune responses and the recognition of threats such as pathogens. Cancer cells alter the expression of certain enzymes, including Sulf-2, which in turn modifies the structure of glycans. This modification helps cancer spread.

"The cells in our body are essentially covered in 'forests' of glycans," said Vitor Pomin, associate professor of pharmacognosy. "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."

Using both computer modeling and laboratory testing, the research team found that the sugar – fucosylated chondroitin sulfate – from the sea cucumber Holothuria floridana can effectively inhibit Sulf-2.

"We were able to compare what we generated experimentally with what the simulation predicted, and they were consistent," said Robert Doerksen, professor of medicinal chemistry. "That gives us more confidence in the results."

Unlike other Sulf-2 regulating medications, the sea cucumber compound does not interfere with blood clotting, said Joshua Sharp, UM associate professor of pharmacology.

"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," he said. "So, it's very promising that this particular molecule that we're working with doesn't have that effect."

As a marine-based cancer therapy, the sea cucumber compound may be easier to create and safer to use.

"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 very expensive," Sharp said. "That's why a natural source is really a preferred way to get at these carbohydrate-based drugs."

Unlike extracting carbohydrate-based drugs from pigs or other land mammals, extracting the compound from sea cucumbers does not carry a risk of transferring viruses and other harmful agents, Pomin said.

"It's a more beneficial and cleaner resource," he said. "The marine environment has many advantages compared to more traditional sources."

But sea cucumbers – some variants of which are a culinary delicacy in the Pacific Rim – aren't so readily abundant that scientists could go out and harvest enough to create a line of medication. The next step in the research is to find a way to synthesize the sugar compound for future testing.

"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 to animal models."

The interdisciplinary nature of the scientific study, which featured researchers from chemistry, pharmacognosy and computational biology, underscored the importance of cross-disciplinary collaboration in tackling complex diseases like cancer, Pomin said.

"This research took multiple expertise: mass spectrometry, biochemistry, enzyme inhibition, computation," Pomin said. "It's the effort of the whole team."

This work is based on material supported by the National Institutes of Health grant nos. 1P20GM130460-01A1-7936, R01CA238455, P30CA51008 and S10OD028623.

Top: A sugar compound found in sea cucumbers could hold the key to stopping the spread of cancer, according to a recent UM-led study published in Glycobiology. Graphic by Stefanie Goodwiller/University Marketing and Communications