A humble sponge in Indonesia may be creating cancer medicine
Most people will know at least one person who has been affected by cancer. Research has come a long way, but cancer treatments still rely primarily on chemotherapy and radiation, two approaches that often reduce quality of life. As cancer diagnoses rise, discovering more effective medicine for localized tumors before they spread becomes drastically important. Many natural sources produce numerous potential medications. As their habitats shrink due to global warming, we might lose these valuable resources.
That’s where a sponge comes in.
While some new cancer medicines are developed in labs, they can also be found in natural sources. More than 49% of currently available anticancer agents come from microbes and plants. Chemical substances produced by living organisms, called natural products, are often more desirable than synthetic drugs. Natural products can have unique structures and they tend to be less expensive and more environmentally friendly. A common way to expose potentially useful medications from the natural world is by tapping into previously unexplored sources — like sea sponges.
Sea sponges are multicellular organisms that are usually fixed to one place on the ocean floor. Like a kitchen sponge, they have bodies full of pores. Water runs through the pores to provide sponges with food and oxygen.
Global collaboration pushing the envelope of cancer research
A collaboration of researchers at the Medical University of South Carolina (MUSC), the University of South Carolina (UofSC), College of Charleston, Gadjah Mada University in Indonesia and the University of Malaya in Malaysia reported on the anticancer activity of manzamine A, a natural product produced by a marine sponge.
Together, the groups isolated manzamine A and tested its effectiveness against multiple cervical cancer cell lines in the lab. Cervical cancer cells are easy to grow and manipulate in the lab, which is why they’re often used for new medicine development. The team also used computer modeling to suggest that new cancer medication may be based on manzamine A.
Marine sponges produce a number of this particular kind of natural product. Manzamine A is characterized by a unique nitrogen-containing ring in the middle of its structure. Though researchers have long known that these products may be useful therapeutics, , few studies have looked at manzamine A in particular as a potential anticancer agent. The authors of this particular study, published in the Journal of Natural Products, not only confirmed that manzamine A is a suitable anticancer agent, but also that its structure could be altered to produce more anticancer medicines.
Calling on nature to treat a devastating disease
In 2003, Scientists extracted and purified manzamine A from the Indonesian sponge Acanthostrongylophora collected from Manado Bay Northern Sulawesi, Indonesia. Because these sponges are immobile, they actually produce a wide range of natural products aimed at protecting them from predators. These products (alkaloids), like manzamine A, are often toxic to living cells. Specifically, manzamine A stops cancer cells from replicating and increases the rate of cell death. This means that alkaloids are good places to look for cancer therapeutics!
Stopping cell growth in its tracks
Cancer progresses through uncontrolled growth and replication of cancerous cells in the body. Researchers normally start investigating potential anticancer drugs by testing whether the potential treatment can slow or stop cancer cell growth. Here, the researchers grew four types of cervical cancer cells and dosed them with various concentrations of manzamine A.
At the optimal dose, the natural product decreased the survival of each type of cell, although it was more effective on some cell types than others, showing less potency on human papilloma virus (HPV) positive cells. HPV is a sexually transmitted disease that causes 70% of cervical cancers. This result means that this natural product might not be as effective for patients with HPV. Such information helps researchers identify the types of patients who would benefit most from this natural product.
Upon closer inspection, researchers saw that treatment of cervical cancer cells with manzamine A reduced the presence of SIX1, a cancer-associated protein that helps tumors grow by recruiting cells and stimulating blood vessel growth. If a cervical cancer patient was found to have especially high levels of this protein, they could also be identified as someone who could benefit from this treatment.
Artificial Intelligence taking tips from nature
The researchers in this study liked what they saw with manzamine A and wondered if they could improve on nature’s design. They used a web-based program called Molecular Networking that streamlines molecular structure data for researchers to quickly and efficiently identify different analogues of a known structure and helps design new compounds with better therapeutic potential.
The researchers inputted molecular structure data from manzamine A and five other natural products found in the sponge. The analysis revealed that there were other features of previously undiscovered structures that may also be beneficial.
Knowing that there are still untapped properties of these already potent anticancer agents, the team believes that the chemicals produced by marine sponges warrant future attention in medicinal chemistry research, especially in relation to diseases such as cancer.
Protecting our ecosystems could mean protecting our health
This study highlights the importance that fragile marine ecosystems may play in our long term health and the health of our family and friends. When devastating diseases occur, even our best treatments often fall short of a painless recovery, which is one of the reasons that medicinal research is so important.
Climate change threatens the diversity of species in marine ecosystems. If these species disappear, we may lose the potential medicines that come with them.
Dev Karan, Seema Dubey, Lucia Pirisi, Alexis Nagel, Ivett Pina, Yeun-Mun Choo, and Mark T Hamann Journal of Natural Products 2020 83 (2), 286-295. DOI: 10.1021/acs.jnatprod.9b00577