Cancer fighter found in marine microbes

U. FLORIDA (US) — A chemical compound made from a type of bacteria discovered in the Florida Keys appears to be effective in fighting colon cancer in preclinical experiments.

The compound—known as largazole because it was first found near Key Largo—inhibits human cancer cell growth in cultures and rodent models by attacking a class of enzymes involved in the packaging and structure of DNA.

Details are published in the Journal of Pharmacology and Experimental Therapeutics.

Researchers believe the discovery will lead to new treatment for the roughly 50,000 people in the United States who get colorectal cancer each year.

In addition to having the marine bacteria as a natural source of the chemical, scientists have also been able to synthetically produce it.

“It is challenging to develop natural marine products into drug therapies due to what is termed the ‘the supply problem,'” says Hendrik Luesch, associate professor of medicinal chemistry at the University of Florida.

“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 compound was discovered in 2008 when researchers were investigating samples of bacteria from the Florida Keys.

Known as cyanobacteria, the microbes have evolved to fend off predators or cope with harsh conditions in a marine environment, employing toxins to aid their own survival.

The toxins are the compounds chemists hope to isolate to create drugs that similarly fend off invading cancers in the body.

The compound inhibits enzymes known as histone deacetylases, or HDACs, which are linked to many diseases and are increasingly viewed as promising for cancer therapy.

Jiyong Hong, assistant professor of chemistry at Duke University, teamed with Luesch to chemically reproduce the compound for further preclinical testing, which indicates it is a potent inhibitor of cancer cells with the right properties 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,” Luesch says.

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

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