New anti-cancer drug maybe from sea algae



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February 11, 2008  
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cyanobacteria.jpgCM NEWS, UCSD release – A team of researchers has identified a potent new anti-cancer drug isolated from a toxic blue-green algae found in the South Pacific.

The properties of somocystinamide A (ScA) are described in a paper that will be published online in Proceedings of the National Academy of Science. The research team was spearheaded by Dennis Carson M.D., professor of medicine and director of the Rebecca and John Moores UCSD Cancer Centre at the University of California, San Diego (UCSD).

What is cyanobacteria? Cyanobacteria, also known as Cyanophyta or blue-green algae, is a phylum of bacteria that obtain their energy through photosynthesis. They are a significant component of the marine nitrogen cycle and an important primary producer in many areas of the ocean, but are also found on land.

Cyanobacteria are proving to be a source of a large number of novel organic compounds with biological activity. Among the many compounds found and characterised to date, many are toxic and have been suspected as the cause of deaths in animals (including humans).

Though cyanobacteria do not have a great diversity of form, and though they are microscopic, they are rich in chemical diversity. Cyanobacteria get their name from the bluish pigment phycocyanin, which they use to capture light for photosynthesis. They also contain chlorophyll a, the same photosynthetic pigment that plants use. In fact the chloroplast in plants is a symbiotic cyanobacterium, taken up by a green algal ancestor of the plants sometime in the Precambrian.

Cyanobacteria are photosynthetic, and so can manufacture their own food. This has caused them to be dubbed “blue-green algae”, though they have no relationship to any of the various eukayotic algae. The term “algae” merely refers to any aquatic organisms capable of photosynthesis, and so applies to several groups.

Cyanobacteria are important in the nitrogen cycle. Cyanobacteria are very important organisms for the health and growth of many plants. They are one of very few groups of organisms that can convert inert atmospheric nitrogen into an organic form, such as nitrate or ammonia. It is these “fixed” forms of nitrogen which plants need for their growth, and must obtain from the soil. Fertilizers work the way they do in part because they contain additional fixed nitrogen which plants can then absorb through their roots.

Cyanobacteria also form symbiotic relationships with many fungi, forming complex symbiotic “organisms” known as lichens.

cyanobacteria1.jpg“We are excited because we have discovered a structurally unique and highly potent cancer-fighting compound,” said Dwayne G. Stupack, associate professor of pathology at the Moores UCSD Cancer Centre. “We envision it will be perfect for emerging technology, particularly nanotechnology, which is being developed to target cancerous tumours without toxic side effects.”

The ScA compound was found in the cyanobacteria L. Majuscula, also known as “mermaid’s hair,” gathered off the coast of Fiji in the South Pacific by the laboratory of William Gerwick at Scripps Institution of Oceanography.

A diverse team of researchers from UCSD’s Cancer Centre, School of Medicine, Skaggs School of Pharmacy and Pharmaceutical Sciences, and Scripps worked to identify, screen and test marine compounds in vitro and in vivo. They found that ScA inhibits neovascularization, the formation of blood vessels that feed tumors, and also had a direct impact on tumour cell proliferation.

“The compound isn’t toxic to the cyanobacteria itself, but activates a ‘death pathway’, present in our cells,” said Stupack. “When the cells of the blood vessels that feed tumours become activated and proliferate, they become especially sensitive to this agent.”

Gerwick noted that if a normal-sized swimming pool full of cancer cells were treated with ScA, it would take only three milligrams – about the weight of a grain of rice – to kill all of the cancer cells.

Wolf Wrasidlo, Ph.D., senior project scientist at the Moores UCSD Cancer Centre and first author of the work, added that the unique structure of this compound lends itself very well to nanotechnology, because it “incorporates spontaneously” into molecule-sized nanoparticles, important for the kind of highly targeted, combination therapy being developed to treat cancer. The structure is also simple enough that the scientists can reproduce it.

“ScA is the first, and most potent compound we’ve identified so far,” Stupack said, adding that it won’t be the last, as the Scripps team has identified more than 250 unique compounds from L. Majuscula alone. “But we don’t yet know how abundant ScA is, or if it’s feasible to harvest, so it is important that we have been able to produce this natural product in the lab.”