Compound Discovered in Florida Keys Shows Potential as Colon Cancer Treatment

A chemical compound made from a type of bacteria discovered in the Florida Keys (USA) by a pharmacy researcher has shown effectiveness in fighting colon cancer in preclinical research.

Writing online October 2010 in the Journal of Pharmacology and Experimental Therapeutics, scientists from the University of Florida (UF; Gainesville, USA) reported that the compound--known as largazole because it was first discovered near Key Largo--suppresses human cancer cell growth in cultures and rodent models by attacking a class of enzymes involved in the packaging and structure of DNA.

More research is needed, but scientists hope that the finding will lead to new treatments for the about 50,000 people struck with colorectal cancer each year in the United States. Researchers are enthusiastic because in addition to having the marine bacteria as a natural source of the chemical, they have been able to produce synthetically the active chemical compound extracted from the bacteria.

"It is challenging to develop natural marine products into drug therapies due to what is termed the ‘the supply problem,'” said Dr. Hendrik Luesch, an associate professor of medicinal chemistry in the UF College of Pharmacy. "We have solved the supply problem for largazole because it has a relatively simple structure, which has made it easy to reproduce in the lab.”

The Luesch lab discovered largazole while studying samples of bacteria from the Florida Keys, publishing the finding in 2008. Known as cyanobacteria, the microbes have evolved to fend off predators or deal with harsh conditions in a marine environment, employing toxins to aid their own survival. The toxins are the compounds chemists such as Dr. Luesch desire to isolate and understand in a quest to create drugs that similarly fend off invading cancers in the body.

Since the discovery, Dr. Luesch's lab determined the compound inhibits enzymes known as histone deacetylases (HDACs), which are linked to many diseases and are increasingly viewed as promising for cancer therapy. Dr. Jiyong Hong, an assistant professor of chemistry at Duke University (Durham, NC, USA), teamed with the UF researchers to chemically reproduce the compound for additional preclinical testing, which indicates it is a potent inhibitor of cancer cells that has the right characteristics to reach its intended target without the toxic side effects of many cancer drugs.

"Knowing HDAC is the target that makes largazole effective means we can predict good drug properties because there are already two anticancer products on the market that work this way,” said Dr. Luesch, who is a member of the UF Shands Cancer Center.

Three important features make this marine compound more promising than other natural products as an effective cancer-fighting drug, Dr. Luesch noted that availability of supply, knowing its mode of action, and the fact that its cellular target is already a known anticancer target known to result in the necessary selectivity for cancer cells over normal cells.

Dr. Luesch presented the study's findings September 9, 2010, at the Marine Drug Discovery Symposium in Pohang, South Korea, and later in Mid-October at the Marine Natural Products Symposium in Phuket, Thailand. The research is planned for publication in the November 2010 issue of the Journal of Pharmacology and Experimental Therapeutics.

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