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04. BIOCHEMICALS AND HUMAN HEALTH

4(a) Biochemical Effects

1.   Ecteinascidin-743 from the tunicate (ascidian), Ecteinascidea turbinata. Ascidians are organisms that include sea squirts, that is, marine chordates that do not develop a vertebral column. International researchers have been testing the effects of some of these biochemicals on cancer cells. Clinical trials have shown that Ecteinascidin-743 has anti-cancer activity in advanced, sarcoma patients and also against osteosarcomas. Sarcomas are cancers in fat, muscle, bone or cartilage and osteosarcomas are in bone tissue.

Further studies showed that this chemical has an anti-mitotic effect. That is, it stops microtubules forming in cancer cells and these are needed for normal mitotic cell division and tissue growth. If tumour cells are unable to undergo mitosis, then the growth of the tumour is prevented.

This is one international example of a marine natural product approaching a commercial, clinical application.

Cancer cell undergoing normal mitotic division
Cancer cell undergoing normal mitotic division showing cytoskeleton spindles formed with chromosomes aligned for replication. Image: Dr. Christy Adams, AstraZeneca.
Cancer cell treated with Ecteinascidin
Cancer cell treated with Ecteinascidin (after 24 hrs), with cytoskeleton shattered and thus interrupting normal mitotic division. Image: Dr. Christy Adams, AstraZeneca.

2. Stylissadine A and B – from Stylissa flabellata, a sponge from the Great Barrier Reef. This chemical works against P2X7, a pain receptor. These chemicals, known as P2X7 antagonists, may provide new treatment for inflammatory diseases such as osteoarthritis, rheumatoid arthritis and chronic obstructive pulmonary disease (COPD).

Stylissa flabellata.
Stylissa flabellata. Image: Dr. John Hooper, QM.

3. Psammaplin A and Bisaprasin 11’-sulfatefrom Aplysinella rhax, a sponge from the Great Barrier Reef. This chemical has been found to be effective in controlling blood flow, cardiovascular function and metabolism at the pre-clinical phase of testing.

Aplysinella rhax
Aplysinella rhax, also affectionately known as the ‘dog food sponge’ due to its texture. Image: Dr. John Hooper, QM.

4.  Adociasulfate 1,7,8,9 – from Adocia (=Haliclona) aculeata, a sponge from the Great Barrier Reef. This chemical inhibits a protein pump that is essential for bone resorption cell activity. As the calcium in the bone is not re-absorbed as much, it stays in the bone and therefore it may help with controlling osteoporosis.

Haliclona aculeata, an encrusting sponge
Haliclona aculeata, an encrusting sponge growing on a whip-coral, Junceela sp. Image: Dr. John Hooper, QM.

5. Dysinosin A – from a new species and genus of sponge, Citronia astra, from the outer Great Barrier Reef. This chemical is a hypothetically ideal drug candidate due to its small chemical structure. It is thought to be effective in oncology (cancer treatment) and various trials are currently underway. Another compound from this sponge is thought to be effective against human a-thrombin. That is, it would assist in preventing the formation of blood clots in people prone to getting them.

Citronia astra, is only found at specific habitats on the outer reef
Citronia astra, is only found at specific habitats on the outer reef, fore-reef surge zones. It is characterised by a series of convoluted ridges and grows on ‘consolidated pavement’ on the reef flat.  Image: Dr. John Hooper, QM.

 6. Axinellamines B, C and D – from a new species of Axinella sp.1333 from Sydney. This sponge produces a gastric bactericide potentially effective for treatment and prevention of stomach and duodenal ulcers and stomach cancer. Bactericides are chemicals that work against bacteria. Exiguaquinol is another chemical extracted from the sponge species Neopetrosia exigua, found in tropical Australasia. The chemical has a similar function to the chemicals from Axinella.

Axinella sp.1333
New species of Axinella sp.1333 from Sydney.
Image: Dr. John Hooper, QM.
Neopetrosia exigua
Neopetrosia exigua from tropical Australasia.
Image: Dr. John Hooper, QM.

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