Spying on nature: new marine substance with atypical antitumor mechanism of action
To launch the development of lead compound on its basis is not possible yet, because the marine sponge Monanchora pulchra that the natural molecule was isolated from, produces very little of it. Moreover, the natural substance has a too complex formula to be synthetically produced in the laboratory. Thus, new sources of similar compounds are needed. A related article was published in Nature Scientific Reports by researchers of Far Eastern Federal University (FEFU) and PIBOC FEB RAS.
A compound Monachoximicalin C from the marine sponge Monanchora pulchra has shown high antitumor potential in prostate cancer, killing standard chemotherapy-resistant cancer cells. However, it is too expensive to produce this substance via chemical synthesis. Scientists plan to wait and search for a new source of this or a similar substance, from which medicinal molecules can be obtained in greater quantities.
There are precedents available. For example, a very pronouncing drug Trabectidin isolated from marine invertebrates successfully fights soft tissues sarcomas. At first, to get the lead compound tons of ascidian marine invertebrates are required. Then researchers discover a bacterium, which is producing a similar molecule—an antibiotic Cyanosafracin B in abundance for Trabectidine to be synthesized.
"In the case of a sea sponge, we have rather "spied" the presence of the compound in nature with the atypical mechanism of action than discover a new medicinal molecule. Based on this knowledge, we may get a new promising substance in the future," says Sergey Dyshlovoy from the FEFU Laboratory of Biologically Active Substances, who also a senior researcher of the Laboratory of the Pharmacology of A.V. Zhirmunsky National Scientific Center of Marine Biology. "The compound is promising because, first, it exhibits antitumor activity even at very low concentrations, and second, its mechanism of action leads to the so-called non-apoptotic cell death, which is a rather rare combination and may turn out to be an advantage."
The scientist explained that many anticancer substances cause the programmed death of cancer cells. This mechanism is called "apoptosis". On the one hand, the elimination of cancer cells via this mechanism may cause fewer problems to the patients. There are fewer side effects and lower inflammation risk. On the other hand, some cancer types can't be cast off with a such "smooth" scenario. Many tumor types or subtypes have developed resistance to apoptosis. For this reason, more "aggressive" substances are also of interest, although their mechanism of action may fraught with side effects. The good news is, that therapists can rule over the consequences of the "brutal" remedy when developing a general strategy for treating a certain tumour case.
Next, researchers plan to have a close look at the mechanism of action of the new substance.
Monanchora pulchra, a rare sea sponge, was caught in the Russian Far East at a depth of about 100 meters near Chirpoi, the uninhabited Kuril Island, during an expedition on the "Akademik Oparin" research vessel.
The World Ocean studies, including the search for promising medicinal compounds from marine organisms, is one of the priority areas of scientific activity of the FEFU University. The work is carried out in close cooperation with the Institutes of the Far Eastern Branch of the Russian Academy of Sciences.
Recently, scientists of FEFU School of Biomedicine, together with colleagues from the University of Geneva, have been isolated an unusual porphyrin-derivative biologically active substance from Ophiura sarsii marine invertebrate. It has the potential to be utilized as an affordable light-sensitive drug in innovative photodynamic therapy for the targeted treatment of triple-negative breast cancer and other cancers.
More information:
www.nature.com/articles/s41598-020-69751-z
doi.org/10.1038/s41598-020-69751-z
Provided by Far Eastern Federal University
