• Christos Evangelou, PhD

Sponges – the source of anti-cancer treatments?

A recent study shows that the sponge-derived natural compound manzamine A inhibits the growth of cervical cancer cells without affecting healthy cells.

Early diagnosis and prevention owning to Pap tests and HPV vaccination have decreased the number of cervical cancer-related deaths. However, cervical cancer remains the fourth most common cancer in women and a significant healthcare challenge [1].

Researchers from the Medical University of South Carolina (MUSC) investigated the anti-cancer effects of natural products in cervical cancer cells and found that manzamine A inhibited cancer cell growth and promoted cell death without affecting non-cancerous cells. The study was led by Dr. Mark T. Hamann and was published in February 2020 in the Journal of Natural Products [2].

“This is a highly exciting new application for a molecule that has earlier shown significant potential for the control of malaria and has good drug-like properties,” said Dr. Mark T. Hamann, professor in the Department of Drug Discovery and Biomedical Sciences at MUSC and co-senior author of the study. "Natural products have led to the development of most of our antibiotics and anti-cancer therapies and many controls for pain." [3]

This study was a collaborative effort between the Medical University of South Carolina, the University of South Carolina (UofSC), College of Charleston, Gadjah Mada University in Indonesia, and the University of Malaya in Malaysia.

The study also showed that manzamine A decreased the levels of the oncoprotein SIX1. SIX1 is upregulated in various cancers, including cervical cancer, and its expression shortens patient survival. Molecular structure modeling revealed that manzamine A has a similar structure with SIX1 inhibitors, yet manzamine A is ten times more potent in inhibiting SIX1, which could explain its strong anti-proliferative effects.

Manzamine A is a natural compound belonging to a family of unique heterocyclic alkaloids and is produced by marine sponges commonly found in Manado Bay, Indonesia.

"Most of the starting materials for lab-based synthesis are derived from petroleum," Dr. Hamann explained. "In contrast, sponges in their natural habitat can be successfully farmed, and unlike other forms of aquaculture, clean the environment."

Thus, production of these molecules from sponges growing in the environment would likely be the best source while providing opportunities for economic development in rural Indonesia.

"The preservation of species diversity is extremely important, as is the diversity of the chemicals they produce and the opportunities for treating cancer that they offer," explained Hamann. "If 50 years of climate change remains unchecked, projections are that we may lose one-third of the global species diversity. So with that will go opportunities like this."

Another recent study led by Dr. Hamann identified sponge-derived compounds with anti-tumor effects against melanoma, as well as prostate and pancreatic cancers [4]. In experimental animals, Manzamine A has also proven to be effective against Plasmodium, the parasite responsible for malaria [5], making Manzamine A of high clinical interest.

"The goal now is to make sure that it works in animals and then try to advance it into clinical applications and further development," said Dr. Hamann.

Although several lines of evidence from in vitro and preclinical studies in animal models support the potential use of Manzamine A to treat cervical cancer, in addition to other malignancies and malaria, future clinical trials are required to establish its clinical relevance in humans.

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[1] https://www.who.int/cancer/prevention/diagnosis-screening/cervical-cancer/en/ [2] https://pubs.acs.org/doi/10.1021/acs.jnatprod.9b00577 [3] https://www.sciencedaily.com/releases/2020/04/200404155616.htm [4] https://www.frontiersin.org/articles/10.3389/fmars.2020.00058/full [5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC89926/

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