A marine compound discovered off the coast of Key Largo in Florida inhibits cancer cell growth in lab tests and is likely to prompt the development of effective new drugs.
The University of Florida (UF)-patented compound, largazole, is derived from cyanobacteria that grow on coral reefs. It is being described as one of the most promising finds since the college’s marine lab was established three years ago.
The molecule’s natural chemical structure and its ability to inhibit cancer cell growth were first described in the Journal of American Chemical Society in February, and the lab synthesis and description of the molecular basis for its anti-cancer activity appeared on July 2.
“It’s exciting because we’ve found a compound in nature that may one day surpass a currently marketed drug or could become the structural template for rationally designed drugs with improved selectivity,” said Hendrik Luesch, assistant professor in UF’s Department of Medicinal Chemistry and the study’s principal investigator.
Largazole, discovered and named by Luesch for its Florida location and structural features, seeks out a family of enzymes called histone deacetylase, or HDAC. Overactivity of certain HDACs has been associated with several cancers such as prostate and colon tumours, and inhibition of HDACs can activate tumour-suppressor genes that have been silenced in these cancers.
Although scientists have been probing the depths of the ocean for marine products since the early 1960s, many pharmaceutical companies lost interest before researchers could deliver useful compounds because natural products were considered too costly and time-consuming to research and develop.
Many common medications, from pain relievers to cholesterol-reducing statins, stem from natural products that grow on the earth, but there is literally an ocean of compounds yet to be discovered in our seas.
Only 14 natural marine products developed are in clinical trials today, Luesch said, and one drug recently approved in Europe is the first-ever marine-derived anti-cancer agent.
“Marine study is in its infancy”, said William Fenical, professor of oceanography and pharmaceutical sciences at the University of California, San Diego. “The ocean is a genetically distinct environment and the single, most diverse source of new molecules to be discovered”.
HDACs are already targeted by a drug approved for cutaneous T-cell lymphoma manufactured by the global pharmaceutical company Merck & Co. Inc. However, UF’s compound does not inhibit all HDACs equally, meaning a largazole-based drug might result in improved therapies and fewer side effects, Luesch said.
Luesch said that, within the next few months, he plans to study whether largazole reduces or prevents tumour growth in mice. Luesch has several other anti-tumour natural products from Atlantic and Pacific cyanobacteria in the pipeline.
These results were presented on Thursday at an international natural products scientific meeting in Athens.
Sources: The Times Of Imdia