Conservation news

The sponge with the secret recipe: A cancer-fighting chemical

The cancer-fighting marine sponge, A. ingens, is prevalent throughout Indonesia, including in Manado Bay. Image by Sakurai Midori.

  • Scientists have discovered that a common sea sponge growing in Indonesian waters produces a chemical called manzamine A that has been shown to fight cervical cancer cells in the lab.
  • They say that if it can be produced at scale, manzamine A could be used to fight a wider variety of cancers as well as infectious diseases.
  • Cultivating the sponge Acanthostrongylophora ingens at scale would also be beneficial to coastal communities and the Indonesian economy at large, the scientists say.
  • And because the sponge has a high tolerance for poor-quality water, its cultivation can help purify contaminated water, buffer unspoiled reefs from pollution, and otherwise enhance the marine ecosystem.

Throughout the waters surrounding Indonesia, a porous tubular creature sits fixed onto coral reefs, its plain appearance hiding a potentially lifesaving secret.

Researchers recently found that this sponge produces a substance that could fight cancer and other lethal diseases, and they’ve proposed cultivating it to benefit Indonesia’s marine environment and economy.

Acanthostrongylophora ingens yields a molecule called manzamine A, which counters cervical cancer cells in the lab, according to a paper published in the Journal of Natural Products.

Although Pap smears and human papillomavirus vaccines have lowered this type of cancer’s occurrence over the years, it remains the fourth most common in women, with roughly 14,000 diagnoses and more than 4,000 deaths projected in the U.S. alone for 2020 by the American Cancer Society. Manzamine A, which comes from bacteria living in a mutually beneficial relationship with the sponge, has huge implications for stopping this killer because it could restrain aggressive tumors without damaging healthy cells, according to the paper.

“It prevents cell replication rather than killing the cell outright, leading to immediate impacts on tumor growth, and then other drugs are useful for killing remaining tumor cells, or they may die on their own,” said Mark Hamann, a professor with the Medical University of South Carolina’s Department of Drug Discovery and Biomedical Sciences and corresponding author on the study.

“Success in humans remains to be seen, but it seems very hopeful. The agent would reduce toxic side effects, so that’s the greatest utility.”

Through the beneficial bacteria it hosts, A. ingens creates large amounts of manzamine A, a molecule that could stop cancer and other deadly illnesses. Image by Rob van Soest.

Scientists at the Medical University of South Carolina, the University of South Carolina, the College of Charleston, Gadjah Mada University in Indonesia and the University of Malaya in Malaysia analyzed how manzamine A inhibited the growth of cervical, prostate and other cancer cells. They observed that it checked the proliferation of cervical cancer cells but didn’t affect non-cancerous ones. Models revealed that while it looks like other inhibitors of cancer, manzamine A has 10 times the effect on a harmful protein associated with it.

“If it ends up advancing in the control of cervical cancer, I’m certain that it finds applications in other forms of cancer,” Hamann said, particularly those characterized by that protein. “If produced on a large scale, it’s a good candidate for modifying and may find utility broadly in infectious diseases.”

A. ingens fares well even in polluted waters near cities like Manado, on the Indonesian island of Sulawesi, so researchers believe that growing the filter feeder to harvest manzamine A in such coastal areas would boost water quality. Image by Sakurai Midori.

Now the scientists are further testing and developing the compound — which has been shown to cure malaria as well — and determining safety, dosage and administration methods. They plan to conduct clinical trials later on patients who haven’t had any luck with other types of chemotherapy.

Since manzamine A is difficult to create artificially, and sponge aquaculture has proven profitable with bath sponges, Hamann said he recommends growing A. ingens commercially in Indonesian seas to not only obtain the drug but to also improve ecological and economic conditions.

This “very desirable fisheries project,” he said, would involve hanging sponge cuttings from ropes underwater. The filter feeder, which “thrives where water is fairly poor quality and many other species do not survive,” could purify contaminated water, buffer unspoiled reefs from pollution, and otherwise enhance the marine ecosystem. And establishing an industry centered on the sponge would supply extra income to Indonesians, help boost their standard of living, and contribute to the country’s economy.

“Since the sponge produces this molecule in high yields, and it seems easy to grow, you could grow it in polluted waters near wastewater plants or river mouths along the ocean, and it would potentially grow very well,” Hamann said. “It would be a promising economic development tool to put sponge culture facilities where there’s high nutrient loads to improve water quality and build a business around the manufacture of the drug. It’d have a valuable local impact.”

A colorful array of coral inhabits Manado Bay. A. ingens lives on reefs like this. Image by Samuel Chow.

Netty Siahaya, a lecturer at Pattimura University’s School of Mathematics and Natural Sciences and sponge chemicals researcher who wasn’t part of this study, emphasized the vast possibilities of substances like manzamine A, which enable sponges themselves to deal with threats such as viruses.

But she said that “to get the potential of the sponge as a cancer drug, we can take it at locations estimated to be clean compared to locations with very high activities that are likely polluted.” Heavy metals and other contaminants could bind to manzamine A, she said, making it more difficult and expensive to extract.

Like many coastal organisms in Indonesia, sponges have generally declined in recent decades due to habitat-degrading human impacts such as coral extraction and pollution, said Victor Nikijuluw, senior director of Conservation International Indonesia’s marine program.

Culturing sponges for pharmaceuticals and using sponges to gauge ecosystem health would provide greater impetus for the protection of coral reefs as well as the animals themselves, which perform additional services such as carbon regulation, Siahaya said.

“To maintain the existence of sponges, we need to cultivate them and protect aquatic ecosystems,” she said.

Nikijuluw agreed that farming A. ingens “is a nice idea,” especially considering that Indigenous peoples on Indonesia’s eastern islands have long harvested shallow-water sponges for medicinal and other household purposes. He pointed out the gaping lack of information about Indonesian sponges and their useful properties and stressed tapping into traditional knowledge to learn about them.

Marine conservation planning in Indonesia, he said, should no longer disregard sponges.

“We’re relying on the biodiversity of corals to decide if a particular site should be conserved,” Nikijuluw said. “Where you will find a lot of sponge, no corals, if you just focus on coral, you will not conserve … The sponge should be included in the reasoning for conservation.”

Even if A. ingens turns out to be unfeasible for cancer treatment, it should still be conserved, Nikijuluw suggested, perhaps partly through cultivation for another identified use.

Regardless, he said, if “we do not know the benefit of the species to human beings, we cannot conclude that this species doesn’t have any function. Right now, science may not disclose those functions, but later, you’ll understand … If it is has no direct benefit to human beings, it has an indirect benefit through the environment.”

Citation:

Karan, D., Dubey, S., Pirisi, L., Nagel, A., Pina, I., Choo, Y., & Hamann, M. T. (2020). The marine natural product manzamine A inhibits cervical cancer by targeting the SIX1 protein. Journal of Natural Products, 83(2), 286-295. doi:10.1021/acs.jnatprod.9b00577

Banner: The cancer-fighting marine sponge, A. ingens, is prevalent throughout Indonesia, including in Manado Bay. Image by Sakurai Midori.

FEEDBACK: Use this form to send a message to the author of this post. If you want to post a public comment, you can do that at the bottom of the page.