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Metabolites from Marine Microorganisms in Cancer, Immunity, and Inflammation

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Metabolites from Marine Microorganisms in Cancer, Immunity, and Inflammation © 2020 Journal of Pharmacy & Pharmacognosy Research, 8 (5), 368-391, 2020 ISSN 0719-4250 http://jppres.com/jppres Original Article | Artículo Original Metabolites from marine microorganisms in cancer, immunity, and inflammation: A critical review [Metabolitos procedentes de microorganismos marinos en cáncer, inmunidad e inflamación: Una revisión crítica] Mario Riera-Romo, Liem Wilson-Savón, Ivones Hernandez-Balmaseda* Department of Pharmacology, Institute of Marine Sciences, Havana 10600, Cuba. *E-mail: [email protected], [email protected] Abstract Resumen Context: Marine microorganisms represent a promising source of Contexto: Los microorganismos marinos constituyen una fuente de bioactive molecules for biomedical applications. Increasing scientific moléculas bioactivas para aplicaciones biomédicas. En la literatura se literature is describing novel metabolites isolated from marine microbes han descrito metabolitos novedosos aislados de microbios marinos con with attractive pharmacological properties, such as anti-inflammatory, propiedades farmacológicas atractivas como anti-inflamatoria, immunomodulatory, and anticancer. inmunomoduladora y anticancer. Aims: To reveal a background of the main marine microbial-derived Objetivos: Revelar estado del arte de los principales productos derivados products that have been isolated and characterized, including recent de microbios marinos que han sido aislados y caracterizados, examples. The main mechanisms of action of these compounds in incluyendo ejemplos recientes. También se discuten los principales different models are also discussed. mecanismos de acción de estos compuestos en diferentes modelos. Methods: This research was structured based on a four phases design. 1) Métodos: Esta investigación fue estructurada en un diseño de cuatro the identification of research questions, 2) selection of relevant studies, fases. 1) Identificación de las preguntas de investigación, 2) selección de 3) filtering of studies based on inclusion and exclusion criteria, and 4) los estudios relevantes, 3) filtrado de los estudios basado en los criterios collection and organization of the data. For the web search, were used de inclusión y exclusión, y 4) colección y organización de los datos. Para PubMed, Web of Science, Science Direct and ProQuest. For the selection la búsqueda en la web se utilizaron PubMed, Web of Science, Science and classification of the papers was used PRISMA software. Direct and ProQuest. Para la selección y clasificación de los artículos se Results: A wide variety of marine microbial metabolites with important empleó el software PRISMA. pharmacological properties have been discovered and characterized so Resultados: Una amplia variedad de metabolitos derivados de microbios far. The main sources of these compounds are marine actinomycetes, marinos con propiedades farmacológicas importantes han sido bacilli, fungi from Aspergillus and Penicillium genus, microalgae, and descubiertos y caracterizados hasta la fecha. Las principales fuentes de some marine symbiotic bacteria and fungi. Most of these metabolites estos compuestos son los actinomicetos marinos, bacilos, hongos de los exhibit cytotoxic, pro-apoptotic, anticancer, anti-inflammatory, and géneros Aspergillus y Penicillium, microalgas y algunas bacterias y immunomodulatory activities. Complex structural moieties, such as hongos simbióticos. La mayoría de estos metabolitos exhiben actividad multiple aromatic rings and heteroatoms, seem to be related to these citotóxica, pro-apoptótica, anticancer, anti-inflamatoria e properties. The mechanisms of action of most of these molecules target inmunomoduladora. Motivos estructurales complejos como múltiples apoptosis-related proteins, enzymes, transcription factors, DNA binding anillos aromáticos y heteroátomos parecen estar relacionados con estas proteins and some cell surface receptors. propiedades. Los mecanismos de acción de casi todas estas moléculas Conclusions: The marine environment offers an efficient and attractive tienen como blanco proteínas relacionadas a la apoptosis, enzimas, way to obtain novel natural products. Marine microorganisms are a factores de transcripción, proteínas de unión al ADN y algunos prolific source of new molecules and extracts with therapeutic potential receptores de la superficie celular. in the treatment of chronic inflammatory diseases. They represent and Conclusiones: El medioambiente marino ofrece una vía atractiva y ecofriendly and feasible option to obtain drug candidates with multiple eficiente de obtener novedosos productos naturales. Los mechanisms of action and important biomedical applications. microorganismos marinos son una fuente prolífica de nuevas moléculas y extractos con potencial terapéutico en el tratamiento de enfermedades inflamatorias crónicas. Ellos representan una opción ecológica y factible para obtener nuevos candidatos a fármacos con múltiples mecanismos de acción e importantes aplicaciones biomédicas. Keywords: bioactive compounds; biomedical applications; cancer; Palabras Clave: aplicaciones biomédicas; cáncer; compuestos bioactivos; inflammation; immunity; marine microorganisms. inflamación; inmunidad; microorganismos marinos. ARTICLE INFO Received: September 16, 2019. Received in revised form: March 5, 2020. Accepted: April 6, 2020. Available Online: April 18, 2020. Declaration of interests: The authors declare no conflict of interest. Funding: This work has been supported by the Agency of Environment, CITMA, Cuba (project P211LH005-016). _____________________________________ Riera-Romo et al. Marine microorganism metabolites in cancer, immunity, and inflammation INTRODUCTION structures with high pharmacological potential (Hasan et al., 2015; Vijayakumara and Muniraj, Nowadays, the search for novel pharmacologi- 2015). Moreover, microbes associated with macro- cally active compounds has been focused on natu- organisms, such as marine plants and animals, are ral products because they are an effective and less emerging as an interesting source of new bioactive toxic alternative to synthetic drugs (Mouhid et al., compounds (Penesyan et al., 2011; Mazard et al., 2017). Marine microorganisms, in particular, be- 2016). cause of their abundance and diversity, are a promising source of bioactive substances for bio- Terrestrial plants have been used for centuries medical applications (Bhatnagar and Kim, 2010). in the treatment of human diseases, whereas the exploration of microorganisms as a source of ther- These species live in stressful conditions such as apeutical compounds has a relatively short history poor light, high pressure, and cold temperatures, (Monciardini et al., 2014). In spite of that, more which stimulate the production of many second- than 10% of the current natural bioactive products ary metabolites that serve as a chemical defense have a microbial origin (Hegazy et al., 2015). The against adverse environmental conditions huge biomedical potential of marine microorgan- (Bhatnagar and Kim, 2010). In addition, they pro- isms remains mostly unexplored, and the wide duce toxins, pigments, and a variety of chemical chemical diversity of these microbial-derived compounds that possess a different degree of bio- products offers the possibility to modulate multi- activity against other microorganisms. It has been ple molecular targets (Penesyan et al., 2013; Hasan proven that these molecules have therapeutic ap- et al., 2015). This review intends to highlight the plications and exhibit important pharmacological pharmacological potentials of the main groups of properties, including antimicrobial, cytotoxic, pho- marine microorganisms and their derived prod- to-protective, anti-inflammatory, and anticancer ucts/compounds in different pro-inflammatory (Bhatnagar and Kim, 2010). They are able to modu- and immunopathological conditions, including late different cellular targets like enzymes, mem- cancer. brane receptors and transcription factors, covering a broad spectrum of action mechanisms (Steven- METHODOLOGY son et al., 2002; Toledo et al., 2014; Shin et al., 2016; Xu et al., 2016). Study design Among the main groups of microorganisms, The present research was structured based on a there are bacteria, fungi, microalgae, and symbi- four phases design, including the identification of otic microorganisms. More than 20 000 bioactive research questions, selection of relevant studies, metabolites produced by marine microorganisms filtering of studies based on inclusion and exclu- have been reported, and almost 10 000 are derived sion criteria, and collection and organization of the from actinomycetes, mainly of Streptomyces species data. The four phases were organized as follows (Berdy, 2005). Most of these metabolites are potent (Fig. 1): antibiotics; thus, streptomycetes have become a Phase 1 The research questions and objectives primary source of natural antibiotics for pharma- were established based on the critical review of ceutical and industrial applications (Berdy, 2005). crucial findings and experimental insights in the A deeper exploration of actinomycetes from a ge- field of marine pharmacology for cancer, immuni- netic perspective and the use of high-throughput ty, and inflammation. screenings have allowed the discovery of several novel compounds with different biological activi- Phase 2 The relevant papers were identified ties (Olano et al., 2009a;b). Other groups of marine and collected by searching the keywords related to microorganisms like fungi and cyanobacteria are marine microbial pharmacology
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