Potent cancer fighter lies in Keys algae beds

http://www.sun-sentinel.com:

KEY LARGO Researchers working to conquer one of the nation’s deadliest cancers think they may have found a silver bullet in what might seem a most unlikely place: the blue-green algae beds of Pickles Reef, off the coast of Key Largo. Meanwhile, an Islamorada inhabitant, the bright orange, two-inch-long cone snail, could become a best buddy to smokers trying to quit. The snail’s venom, a paralyzing potion, contains a compound that appears to short-circuit nicotine’s addictive spell.

Who knew that plants and animals indigenous to the Florida Keys are such a promising contributor to the nation’s medicine cabinet?

Actually, to researchers in the field, many of them in Florida labs, it all makes perfect sense.

“People really are recognizing the potential of the ocean,” said Valerie Paul, head scientist at the Smithsonian Marine Station in Fort Pierce.

Ancient civilizations learned thousands of years ago how to use plants and other land-based organisms for curative purposes. Today’s medicinal arsenal includes aspirin from the bark of a willow tree, antibiotics from bacteria, morphine and codeine from opium poppies and penicillin from mold.

But the seas, although they cover 80 percent of the planet, have been a relatively untapped source of compounds to create new drugs.

So far, only two marine-based drugs have been approved by the U.S. Food & Drug Administration: Prialt and Yondelis.

Prialt, a non-narcotic pain-killer derived from the venom of another species of cone snails, is used to treat severe chronic pain in people who cannot use or do not respond to standard pain-relieving medications. It works by blocking pain signals from thenerves to the brain.

Yondelis, made from compounds extracted from orange sea squirts, which look like a bouquet of tiny balloons and grow on the roots of mangroves in the Florida Keys, is used to treat advanced soft tissue sarcoma (a form of cancer) in Europe, Russia and South Korea.

THE FDA OK

Although developed in the United States, Yondelis has yet to receive FDA approval for treatment of sarcoma. It is, however, approved for women with relapsed ovarian cancer.

David Newman, chief of the natural products branch at the National Cancer Institute, said to expect more drugs from the sea in the future.

The reason: small marine life with no physical defenses have developed chemical compounds not found on land to help them fend off ocean predators.

“A sponge can’t swim. Has no teeth,” Newman said. “What does he use for defense? Chemistry. Chemical warfare is a live and well on a coral reef.”

In the pharmaceutical pipeline, many isolated chemical compounds extracted from marine organisms are being researched and tested on rodents and humans.

One is largazole, a compound extracted from blue-green algae and named partly after the place it was first found: Key Largo. It has shown great potential in the fight against colon cancer, the fourth deadliest form of the disease in the United States, according to Hendrik Luesch, a professor of medicinal chemistry at the University of Florida who named the compound and is testing it.

Paul, of the Smithsonian Marine Station, first collected the specific blue-green algae that contained the compound largazole while diving Pickles Reef in 2003.

“It looks like a little fluffy ball of cotton, reddish gold in color,” she said. “Most people would look at it and not think too much about it.”

That sample was one of many different types of seaweed-like blue-green algae that Paul collected. They were not chemically analyzed until Luesch moved to Florida in 2005 and opened the University of Florida’s natural marine products lab the following year.

Lab students isolated the chemical compounds from the different algae. One extract proved especially potent and became the UF-patented largazole.

Luesch screened the compound against 60 different cancer cell lines, and found the colon cancer cell lines were particularly susceptible. It also showed promise against melanoma and renal cancer.

One challenge of developing natural marine products into drugs is the lack of supply. But Luesch teamed up with Jiyong Hong, an assistant professor of chemistry at Duke University, who was able to chemically reproduce the compound in just months.

“Often times it takes years to complete the synthetic version,” Luesch said.

Two years of testing has shown it inhibits cancer cells in mice and human cancer cells grown in cultures.

“At this moment it has potential,” Newman said. “But like a horse at a steeplechase, there are increasingly difficult fences to jump.”

Luesch’s work, funded in part by stimulus money, will be featured on the cover of November’s Journal of Pharmacology and Experimental Therapeutics.

“It takes on average 15 years to develop a drug start to finish,” he said. “We have a long ways to go.”

Frank Mari, professor of biochemistry at Florida Atlantic University, has a grant from the National Institute of Health to study the medicinal qualities of cone snails.

BENEFICIAL VENOM

The small creature’s venom, known to have killed humans, is a mixture of compounds that interact with the central nervous system.

Already the venom from one of the approximately 1,000 different varieties found worldwide has been use to formulate Prialt, approved by the FDA in 2004.

“It’s the most powerful painkiller known to date and is a morphine replacement without causing addiction to morphine,” Mari said.

A different species of cone snail collected off Islamorada has been found to block the neurons involved in nicotine addiction, Mari said.

As for Yondelis, the seeds of its development were sewn back in 1967, when researchers at the University of Miami found that a compound in sea squirts stopped the growth of cancer tumors in nine of 10 mice.

But the discovery had little practical application until scientists could “crack the structure” of the compound. Amy Wright, a research professor at FAU’s Harbor Branch Oceanographic Institute, was involved in doing just that when she was a researcher at a little company called Seapharm Inc. Years later, Yondelis was the result.

“The ocean is full of things to investigate,” Luesch said. “We have only scratched the surface . . . The opportunities for marine drug discovery are tremendous. I’m certainly a believer.”

 

The Tempest: North American Premiere/NYFF Red Carpet – 10.2.10

 

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The 48th New York Film Festival Centerpiece Selection North American Premiere of:
Julie Taymor’s The Tempest

Renowned for her wonderfully inventive works for both stage and screen, Julie Taymor has applied her considerable talents to this fascinating rendering of Shakespeare’s late, great mystical romance. Exiled on a remote island, Prospera (Helen Mirren, extraordinary), the duchess of Milan, conjures up a storm to lure a bevy of characters from her past to shore, revealing in the process a skate of human frailties, illusions, kindness and nobility.

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