Contribution of Prof. Manuel A. Freire-Garabal at UC Berkeley

Seawater Microalgae: A Promising Source Of New Anticancer Drugs

Author: Prof. Manuel A. Freire-Garabal
Full Professor of Medicine. Director of SNL Lennart Levi Lab. University of Santiago de Compostela (Spain)   Oceans occupy 70% of the Earth’s surface. Although there is an enormous biodiversity in the seawater, where approximately 80% of the organisms live, most of its resources are still unexplored, especially invertebrates containing compounds with potent pharmacological properties than those of terrestrial origin. These unique chemical structures result from millions of years of the evolution of these species having to adapt their secondary metabolism to stressful and changing ecosystems.   Starting in the second half of the 20th century, the search for drugs has become one of the most promising directions of marine science. Since FDA approved the synthetic version of cytarabine (originally found the Caribean sponge Tectitethya crypta) in June 1969  for the treatment of patients with leukemia, a small, but growing number of robust marine drugs – like eribulin mesylate, brentuximab vedotin or trabectidineare – are being prescribed in oncology, and more than a dozen of novel marine compounds are used in clinical trials.   Microalgae are intracellular organisms present in different aquatic environments and represent up to 40% of global primary productivity. As they present high photosynthetic efficiencies, microalgae have a high capacity to proliferate at high speed, with relatively simple growth needs and negative balance of CO2, facilitating significant scale cultures that provide high amounts of biomass useful to produce biofuels, food for human or animal nutrition, cosmetics, and a variety of chemicals with different applications including pharmaceuticals. Many of these compounds have selective reaction capacity to many molecular targets, including anticancer properties. Some estimates suggest that 1.8% of natural extracts of marine origin could contain anticancer principles, compared to 0.4 of those on land.   The mechanism of action of microalgae derivates against cancer is complex because they produce concentrations of different isoforms of phytochemicals, which entails multiple interactions. These include cancer cell-selective toxicity and antiproliferative effects, suppression of the metastatic cascade, and blockade of the capacity of solid cancers to stimulate neo-vascularization to support their unlimited capacity to grow.   Other compounds can also intervene in the chemoprevention of cancers, thanks to their immunoenhancing, antioxidant or anti-inflammatory properties. Epidemiological studies have indicated that up to 25% of diagnosed tumors present in their origin a chronic inflammatory process associated with bacterial (i.e., Helicobacter pylori in the case of digestive cancers), viral (i.e., Human Papilloma Virus in cervix cancers), chemical (i.e., tobacco in lung cancer) or physical factors (i.e., UV radiation as a cause of skin cancers). These extrinsic agents, can facilitate the expression of oncogenes or induce mutations in tumor suppressor and DNA repair genes, facilitating induction and progression.   Microalgae are also becoming biotechnology instruments that can displace mammalian cells in the production of recombinant proteins like antibodies, enzymes, immune regulators, vaccines, and other valuable products for cancer prevention or treatment.   Moreover, genetically engineering diatom algae, which have a skeleton made of nanoporous hydrated silicon dioxide (like some nanoparticles used in medicine), have been tested as drug carriers expressing surface antibodies capable of binding cancer cells and delivering chemotherapeutics on-site selectively.