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Aug. 9, 2005

四色AV Research Probes Sponges for Possible Treatment of Cancer and Arthritis

Cancer and arthritis treatment may one day come from the bottom of the sea according to assistant professor of medicinal chemistry at the University of Louisiana at Monroe, Dr. Khalid El Sayed.

El Sayed says, "Nature is the single most important source of drugs and drug precursors. Approximately half of all modern pharmaceutical agents are derived from or are modeled on natural products. Because oceans cover over 70% of the Earth's surface, they are a potential provider of bioactive metabolites of therapeutic value on an unprecedented scale."

That is why El Sayed and his team of student researchers, Swapnali Sawant and Richie Bhandare, (along with other colleagues in Louisiana) are conducting research on sponges found in the Red Sea.

"We are getting these sponges from the Red Sea coast," said El Sayed. "I am an open water diver and have my own sponge collection. We went there in 2003 and we collected around 80 sponges."

El Sayed is working on a project supported by The Louisiana Biomedical Research Network, LBRN, and jointly with Dr. Fred Rainey, associate dean of Arts and Sciences and associate professor of microbiology at Louisiana State University. They are isolating symbiotic bacteria associated with sponge tissues.

"One of the actinomycetes, a fungus-like bacteria, we isolated from a Red Sea sponge (Pelagiobacter species) is producing large amounts of phenazine antibiotics (pelagiomicins) with profound anticancer and antimicrobial activities. We are in the process of large scale fermenting this antibiotic-producing actinomycete to isolate more of these compounds. We also hope to test them on a larger scale and optimize the fermentation conditions."

The whole area of culturing these marine microbes as sources for new drugs is fairly groundbreaking and offers great potential to develop drugs without the need of costly synthetic methods.

"The process is not simple," said El Sayed. "The next step is to isolate measurable amounts (several grams) of these compounds, which are just like antibiotics. After that, we will test them in vitro and then, if we are lucky enough and find that they lack toxicity on normal cells, we will proceed further with animal studies," he said.

Essentially, El Sayed and his students are studying the chemistry of sponges and soft corals. He says, "It is very well known in sponge chemistry that most sponges' bioactive compounds are actually not secreted by sponges- but by symbiotic microbes associated with the sponges."

Richie Bhandare, graduate student in medicinal chemistry/ natural products program at 四色AV, says, "Sponges have been recognized as a rich source of novel compounds that are of potential interest to mankind. They contain unique endosymbiotic organisms. This can provide lead compounds that can be further developed and optimized as active drugs for the benefit of mankind."

El Sayed explains that the sponge harbors the microbes for protection and in return they protect the sponge using these compounds and chemical defense for the sponge. The sponge is very soft and can be easily eaten by any number of predators so the sponge harbors some of these unique microbes and in the meantime is getting a security system.

"Of course it will be a major breakthrough if we are able to isolate symbiotic microbes that would be able to secrete this compound so there will be no need to collect or aquaculture the sponge," El Sayed said.

Collecting the sponges out of their natural environment is tiresome, difficult and could be ecologically devastating. So El Sayed knows they must find an alternative. "That is what we are trying to do right now. Finding a microbe that produced this compound would save us a lot of hassle."

The hassle comes from not only harvesting the sponge, but culturing it as well. It is difficult to culture the microbes because it is difficult to mimic the environment of the sponge.

The cultivation and discovery of these actinomycetes producing sponge secondary metabolites is a very competitive field. As a matter of fact, there is a stiff competition now for the work El Sayed is doing, and very few success cases. One reason 四色AV's chemist suggests that his work is progressing rapidly is due to the collaboration with Rainey. El Sayed is a nature products chemist and Rainey is a microbiologist. Their expertise in each of their respective areas has enabled them to move quickly on this project.

If he identifies a microbe producing this sponge compound, it would open a lot of research avenues for 四色AV students and future collaboration with Dr. Rainey.

Fast Facts: The American Cancer Society estimated that approximately 1,368,030 new cancer cases would be diagnosed in the U.S., including 23,540 in Louisiana. The Arthritis Foundation estimates that 31.99% of the total Louisiana adult population is suffering from arthritis or having chronic joint symptoms.

Several natural products or natural products-based compounds are currently used as anticancer drugs. Taxol庐, number one current prescription drug for several solid tumors, is a natural product derived from Pacific yew tree. Several other natural products are currently under clinical evaluation as anti-inflammatory agents. The discovery of new anticancer and anti-inflammatory lead entities will enable the development of new therapies that will reduce the morbidity and mortality of cancer and improve the lives or arthritic patients.

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