The world’s oceans represent a vast and largely untapped source of biodiversity, offering a high probability for the discovery of unique chemical compounds with therapeutic properties. Among these, bioactive molecules found in marine organisms have shown notable anticancer effects.
For instance, cytarabine, a chemotherapy drug used to treat certain types of leukemia, was inspired by compounds found in the Caribbean sponge Cryptotethya crypta. Similarly, miltefosine, a marine-derived lipid, has proven useful in treating skin metastases caused by breast cancer.
Marine environments are a primary source of lipids (commonly referred to as “fats”) with antitumoral properties. These marine lipids can be used in two complementary ways. The first is nutritional, particularly via dietary intake. The second is based on the development of lipid anticancer agents whose molecular structures are derived from or inspired by the marine environment.
Targeting cancer cells and tumor environments
In both of these approaches, marine-derived lipids are used to selectively target components of the cancer cells or the tumor microenvironment. This addresses both the patient’s overall health and the tumor itself. It works to prevent or inhibit tumor growth, sensitise tumor cells to anti-cancer treatments such as chemotherapy, radiotherapy and immunotherapy, and reduce cancer-related malnutrition.
Dietary factors can thus influence cancer development by either stimulating or inhibiting tumor progression. Reducing the intake of foods containing tumor-promoting components while increasing consumption of those with proven inhibitory effects could delay the onset of various types of cancer.
Marine-derived sources of omega-3 fatty acids
Marine-derived lipids include omega-3 polyunsaturated fatty acids, found in abundance in oily fish such as sardines, mackerel, and herring. They also include ether lipids, present in marine sources such as shark liver oil and scallops.
These different types of lipids – polyunsaturated fatty acids contained in phospholipids and ether lipids – are essential components of cell membranes, particularly in cancer cells. Within tumor environments, these lipids and their derivatives can also modulate signalling pathways involved in tumor development.
At the Inserm-University of Tours research laboratory, “Nutrition, Growth and Cancer”, we are investigating the impact of lipids on cancer at molecular and cellular levels. Our research focuses on how lipids influence processes such as cancer cell growth, proliferation, migration and invasion, as well as how they affect the response to cancer cell treatment.
The antitumor effects of fatty acids in breast cancer, prostate cancer and leukemia
A number of marine-derived lipids and lipid classes, with both anti-tumor and pro-tumor properties, have been identified in recent years. These lipids integrate into cell membranes, where they target specific proteins (the ion channels), influencing the behaviour of cancer cells.
Among these lipids, omega-3 fatty acids, such as eicosapentaenoic acid (EPA), are associated with less aggressive prostate cancer. Specifically, EPA inhibits a complex mechanism involving the SK3 channel, linked – among other things – to cancer cell migration and tumor aggressiveness, and the development of metastases.
Similarly, low levels of EPA and another omega-3, docosahexaenoic acid (DHA), are associated with severe forms of breast cancer, including multifocal breast cancer (characterised by multiple tumors in the same breast), inflammatory breast cancer and premenopausal breast cancer with bone metastases.
Studies conducted by our teams have also demonstrated the therapeutic potential of omega-3 DHA and EPA in the management of leukemia. Clinical trials have since confirmed that these fatty acids may be administered safely to newly diagnosed patients with high-risk leukemia, without compromising the effectiveness of chemotherapy.
Additionally, studies on animals suggest that omega-3 fatty acids may delay cancer-induced malnutrition. These studies must be confirmed on humans.
Across these various cancers, the presence of marine-derived lipids such as omega-3 EPA and DHA have been linked to less aggressive forms of cancer. These lipids are thought to have an antitumor effect.
Future directions: omega-3 supplements combined with treatment?
The molecular impact of omega-3 fatty acids in cancer therapy remains underexplored, but early studies on dietary supplements in cancer prevention have shown promising results. For example, a trial conducted by our team at the University of Tours research lab has demonstrated that combining omega-3 DHA supplements with chemotherapy improves survival outcomes for patients with metastatic breast cancer.
In addition to omega-3 fatty acids, our research has identified two endogenous lipid classes – alkyl and alkenyl lipids (collectively known as plasmalogens) – which appear to be more prevalent in cancer cells than non-cancerous tissues. These lipids are found in the cell membranes near the SK3 channel, a protein which, as mentioned earlier, is linked to cancer cell migration.
Our recent findings shed light on the distinct roles of these endogenous lipid classes. Alkenyl lipids were found to reduce cancer cell aggressiveness by inhibiting the SK3 channel. In contrast, alkyl lipids had the opposite effect, activating the SK3 channel and promoting cancer cell migration.
These findings open new avenues of investigation for targeting cancer cells, which exhibit higher levels of both of these endogenous lipids in comparison with healthy tissues.
Increasing alkenyl lipid levels, known to reduce cancer cell aggressiveness, presents a promising strategy. These marine-derived lipids could be synthetically produced as future anticancer drug components.
One such example is Ohmline, a synthetic derivative of ether lipids with strong therapeutic potential. Recently commercialised by Lifesome Therapeutics, Ohmline has been shown to decrease SK3 channel activity, thereby inhibiting the development of metastases and reprogramming monoclonal antibody responses.
This lipid derivative is therefore being evaluated as a chemotherapy adjuvant for the prevention of neuropathy, a common and debilitating side effect of certain cancer treatments.
Increasing the potential of marine products
Marine products offer a vast spectrum of applications, from serving as models for drug discovery to providing innovative cancer treatments.
The anticancer potential of marine-derived compounds has been demonstrated in numerous studies, including our research within the framework of the Molécules Marines, Métabolisme et Cancer du Cancéropôle Grand-Ouest network. These findings underscore the potential of bioactive molecules from marine environments in developing preventive and therapeutic cancer strategies.
We already have some encouraging data on cancer prevention using various families of lipids of marine or synthetic origin, which can be proposed as sensitising agents for chemotherapy, radiotherapy and therapeutic antibodies.
This article draws on research conducted by the Niche Nutrition Cancer & Oxidative Metabolism (N2COx) team at the University of Tours.
This article is part of the Science Festival (October 4–14, 2024), for which The Conversation France is a partner. This year’s theme, “Ocean of Knowledge,” highlights critical marine issues. Learn more about the festival at Fetedelascience.fr
