Ophiura from Russky Island might make photodynamic therapy more affordable

February 08, 2021

An unusual biologically active porphyrin compound was isolated from seabed dweller Ophiura sarsii. The substance might be used as an affordable light-sensitive drug for innovative photodynamic therapy and for targeted treatment of triple-negative breast cancer and some other cancers. Researchers from the School of Biomedicine of Far Eastern Federal University (FEFU) and the University of Geneva reported the findings in Marine Drugs.

The seabed dweller Ophiura sarsii, the source of the new compound, was isolated at a depth of 15-18 meters in Bogdanovich Bay, Russky Island (Vladivostok, Russia). Ophiuras may resemble a starfish, however, these are two completely different classes, belonging to the type of echinoderms. Recognized back in 1855, O. sarsii is an abundant inhabitant of ocean shallows and at depths. This abundance renders the species as a natural source of a strong medicinal compound with little risk of the species extinction. It's also easy to collect compared to the deep-sea species of this group of marine life.

Initially, biologically active molecules from O. sarsii were scrutinized for the ability to suppress the development of triple-negative breast cancer cells. After the antitumor effect confirmed positive, scientists became interested in the compound's formula. They were surprised when it turned out to represent a variant of a compound class known as porphyrins, that had previously been obtained only through complex artificial synthesis. From Ophiuras, it in contrast can be obtained in just one step without expensive technological processes.

"The compound belongs to the group of porphyrins, substances that previously have never been found in the Ophiurae. It has not been previously identified in natural sources but instead has been only obtained through organic synthesis. In photodynamic therapy, porphyrins can be applied as photosensitizers, agents that, when induced by laser, release active oxygen that kills tumor cells, minimally affecting the rest of the body. Photodynamic therapy was introduced to treatm cancer of the bladder, esophagus, lungs, and basal cell carcinoma. Now it is also used for various dermatological procedures". Explains Vladimir Katanaev, the leading author of the study, Head of the Laboratory of the Pharmacology of Natural Compounds, FEFU. "Artificial synthesis of photosensitizers and, in particular, porphyrin is quite expensive. That makes scientists around the world look for new sources of such compounds. We managed to obtain one by a simple method from a natural source. This discovery might further the biomedicine and, in particular, the developments in the field of targeted anti-cancer therapy based on natural compounds."

The study includes evaluation data for the market of photodynamic therapy pointing out that it could reach nearly $12 billion by 2027. While so, the market depends on a very limited set of therapeutic compounds. New sources of photosensitizers will help expanding the therapy options and make the procedure more affordable.

"Molecules of the porphyrin group were also detected in other marine organisms. For example, in dinoflagellates, the algae that are to blame for the notorious red tides that kill all life. However, a medical version of the substance from them was never attempted to be developed. If and when the medical efficacy of the substance we have discovered is proven, it is quite possible to scale up its production from Ophiurae via mariculture methods, or by optimizing the existing synthesis methods on the basis of the natural compounds to simplify and make them cost-effective," says Vladimir Katanaev.

Natural compounds from Ophiura also demonstrate a strong potential of blocking the WNT-signaling pathway in tumor cells. This pathway' activity is extremely important at the stage of human embryonic development, but their restart in adults is one of the reasons for the development of a triple-negative form of breast cancer, colon cancer, and some other tumors. Scientists will investigate the anti-WNT potential of new compounds from Ophiurae at the next stages.

It remains to be seen whether O. sarsii produces the porphyrin compound on their own or resulting from certain dietary "preferences." Additionally, researchers are interested if the species contains the compound throughout its vast habitat, or it is just a local phenomenon in the region of the Russky Island.

Earlier, scientists from the FEFU School of Biomedicine found that human RSP-12 protein might be a potential target for anti-cancer therapy. For the study, they used the developing eye of Drosophila as a test platform.
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Far Eastern Federal University

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