As our research team continues its ongoing studies of the chemical ecology of Antarctic marine macroalgae and invertebrates we take pride in the applied overtones of our basic ecological research. With pipe lines to the UAB Cystic Fibrosis Center and the National Cancer Institute (NCI), it is a simple step to send these organizations crude organic extracts and pure compounds extracted from the Antarctic marine organisms we are examining in the course of our ecological studies.
After all, it is not hard to imagine that the evolutionary forces that select for novel chemical compounds that deter a predator or prevent smothering by another organism could similarly yield compounds that break down organic materials, or slow or inhibit cell growth. Such outcomes could prove important when seeking new therapeutic drugs to treat diseases such as cystic fibrosis or cancer.
Among the groups of common bottom-dwelling invertebrates that we have been studying in Antarctica are the ascidians or "tunicates", the latter term derives from the outermost body coat or layer known as a "tunic". The swimming "tadpole" offspring of these sponge-like marine organisms bear a close resemblance to vertebrates, but upon metamorphosis into sedentary adults such similarities vanish in an ontogenetic revolution.
As adults, tunicates are vulnerable to mobile predators such as voracious Antarctic sea stars. They lack a hard protective outer shell that would shield against the action of digestive enzymes released by the extruded stomachs of sea stars. As such, tunicates are prime candidates for chemical defenses, and indeed studies in temperate and tropical seas, as well as our own studies in the Southern Sea, have substantiated this theory.
One of the most common tunicates in the vicinity of Palmer Station is known in scientific nomenclature as Synioicum adareanum. In some locations individuals of this colonial species literally carpet the bottom of the sea, numbering in the hundreds and even thousands of individuals. Recently, our Natural Products Chemist and University of South Florida co-team leader, Dr. Bill Baker, along with one of his graduate students, Thushara Diyabalange, discovered a novel chemical in the body tissues of this abundant Antarctic tunicate.
The molecular structure of this compound placed it among a chemical group known to chemists as polyketide amides. Nameless, the new compound was soon christened "Palmerolide", its etiology rooted in both its discovery near Palmer Station, Antarctica, and its unique chemical structure. As with all novel compounds we describe in the course of our ecological studies, we sent it off for routine screening by the NCI.
You can imagine our surprise when scientists with the NCI contacted us several months later to inform us that Palmerolide was both remarkably potent and had highly targeted activity against melanoma, a deadly form of skin cancer. Its high potency was exciting because it was active against melanoma cells at concentrations well below those that would harm non-cancerous cells (an enticing result considering many cancer drugs are also toxic to healthy cells). Its high specificity for melanoma suggested a mechanism of action that had drug development potential.
The NCI next asked us to send them more Palmerolide so they could re-test the pure compound to ensure what they had observed was indeed a dependable result. Re-testing not only verified the potent nature of Palmerolide against melanoma, but expanded its known activity to 4 of 7 different types of melanoma. Currently the NCI is comparing the broad patterns of bioactivity of this compound with patterns of other known toxic compounds to see if this sheds light on just how Palmerolide is able to both inhibit and kill cancer cells.
The NCI is also conducting “tube tests” placing cancerous cells into small porous tubes which are inserted into mice that have been injected with Palmerolide to see if the compound finds its way into the tube-sequestered cancerous cells. Such “delivery potential” is important to ascertain if Palmerolide were to be considered for development into a cancer drug. If all goes well, future studies would develop techniques to synthesize Palmerolide in the laboratory, thus precluding the need to harvest tunicates, an endeavor both commercially infeasible and of potential environmental concern.
Where the study of this unique Antarctic tunicate compound with anti-cancer activity will lead nobody knows. Nonetheless, for the time being we remain excited about this anti-cancer compound discovered mid-stream in the course of our marine ecological studies. Importantly, if a cancer drug were to be developed, it would be yet another example of how the pursuit of knowledge grounded in the basic sciences plays so critically into discoveries with direct applications to humankind.