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Natural compound from a deep-water marine sponge found to reduce pancreatic tumor size

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Scientists at Florida Atlantic University's Harbor Branch Oceanographic Institute found that a deep-water marine sponge collected off of Fort Lauderdale's coast contains leiodermatolide, a natural product that has the ability to inhibit the growth of cancer cells as well as block cancer cells from dividing using extremely low concentrations of the compound. This work resulted in the award of a patent from the U.S. Patent and Trademark Office protecting the use of the compound against various forms of cancer. Sea sponges are an ancient group of animals that appeared more than 600 million years ago that have many of the same genes as humans. These scientists are taking advantage of this similarity in human and sponge genomes to isolate marine natural compounds from these organisms to develop medicines useful in the treatment of human diseases such as cancer. The researchers are expanding on their original findings, recently showing that leiodermatolide can reduce pancreatic tumor size in vivo, publishing the results of this study in the International Journal of Cancer (IJC).

Pancreatic cancer is the fourth leading cause of cancer death in the United States. Pancreatic cancer patients have less than a seven percent survival rate within five years of diagnosis, and 74 percent of patients die within the first year of diagnosis. In recent years, pancreatic cancer has received considerable attention because many well-known individuals have died from the disease. September marks seven years since the passing of actor Patrick Swayze, and October will be five years since the death of Apple Inc. co-founder Steve Jobs. The great tenor Luciano Pavarotti also died from this disease almost a decade ago.

In the article in IJC titled, "Leiodermatolide, a Novel Marine Natural Product, Has Potent Cytotoxic and Antimitotic Activity Against Cancer Cells, Appears to Affect Microtubule Dynamics, and Exhibits Antitumor Activity," the researchers more fully define how this marine compound kills the cancer cells, and show that its effects occur not only against cells but that it also has the ability to reduce pancreatic cancer tumor weight.

Lead author Esther Guzmán, Ph.D., associate research professor at FAU Harbor Branch, along with colleagues and co-authors Amy Wright, Ph.D., research professor; Tara Pitts, biological scientist; and Priscilla Winder, Ph.D., research associate; as well as collaborators from Eisai Pharmaceuticals and the University of Central Florida, have been able to show that leiodermatolide induces programmed cell death in pancreatic cancer cells, and inhibits the growth of other cancer cells such as metastatic melanoma, colon cancer, lymphoma, and glioblastoma, a rare and deadly form of brain cancer.

Taxol™, a commonly used anti-cancer drug, works by interacting with tubulin and causing its polymerization. Leiodermatolide also interacts with tubulin but appears to affect microtubule dynamics through a unique mechanism of action compared to other microtubule interacting agents. In a mouse model of metastatic pancreatic cancer, leiodermatolide exhibited significant tumor reduction when compared to gemcitabine — the standard of care drug for pancreatic cancer — and controls.

"Given the uniqueness of its mechanism of action, its potency, its selectivity for cancer cells, and its in vivo efficacy, leiodermatolide is an extremely interesting compound that merits further studies to determine its therapeutic potential for addressing some of the most devastating forms of cancer," said Guzmán.

Natural products, or secondary metabolites, are small, organic molecules produced by organisms. Unlike primary metabolites such as sugars, fats or proteins, these molecules are not essential to sustain life; however, the compounds are thought to confer an evolutionary advantage to the producing organism. For example, if a sponge makes a compound that is toxic to predators or tastes bad, that sponge may be protected from being eaten, and will have an advantage over one that does not produce the compound. In addition to blocking predation, natural products can have many different functions within the producing organism.

FAU Harbor Branch's drug discovery program, spearheaded by Wright, looks for treatments for pancreatic cancer and infectious diseases, and their scientists also have collaborations with other scientists working on other forms of cancer, malaria, tuberculosis, neurodegenerative disease and inflammation.

"The primary goal of our marine biomedical and biotechnology program is to discover marine natural products with utility as medicines or as tools to better allow us to understand disease processes," said Wright.

The research in this publication was funded by the National Institutes of Health (NIH RO1 CA093455), the State of Florida Center of Excellence in Biomedical & Marine Biotechnology (COE-HRE07), the National Oceanic and Atmospheric Administration (NOAA CIOERT NA09OAR4320073) and the Health Resources & Services Administration Center for Sustainable Use of Marine Resources (4C76HF00231-01-04).

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About Harbor Branch Oceanographic Institute:

Founded in 1971, Harbor Branch Oceanographic Institute at Florida Atlantic University is a research community of marine scientists, engineers, educators and other professionals focused on Ocean Science for a Better World. The institute drives innovation in ocean engineering, at-sea operations, drug discovery and biotechnology from the oceans, coastal ecology and conservation, marine mammal research and conservation, aquaculture, ocean observing systems and marine education. For more information, visit http://www.fau.edu/hboi.

About Florida Atlantic University:

Florida Atlantic University, established in 1961, officially opened its doors in 1964 as the fifth public university in Florida. Today, the University, with an annual economic impact of $6.3 billion, serves more than 30,000 undergraduate and graduate students at sites throughout its six-county service region in southeast Florida. FAU's world-class teaching and research faculty serves students through 10 colleges: the Dorothy F. Schmidt College of Arts and Letters, the College of Business, the College for Design and Social Inquiry, the College of Education, the College of Engineering and Computer Science, the Graduate College, the Harriet L. Wilkes Honors College, the Charles E. Schmidt College of Medicine, the Christine E. Lynn College of Nursing and the Charles E. Schmidt College of Science. FAU is ranked as a High Research Activity institution by the Carnegie Foundation for the Advancement of Teaching. The University is placing special focus on the rapid development of critical areas that form the basis of its strategic plan: Healthy aging, biotech, coastal and marine issues, neuroscience, regenerative medicine, informatics, lifespan and the environment. These areas provide opportunities for faculty and students to build upon FAU's existing strengths in research and scholarship. For more information, visit http://www.fau.edu.

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