{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T08:46:15Z","timestamp":1765356375348,"version":"build-2065373602"},"reference-count":47,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2018,4,27]],"date-time":"2018-04-27T00:00:00Z","timestamp":1524787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Bioprospection of marine invertebrates has been predominantly biased by the biological richness of tropical regions, thus neglecting macro-organisms from temperate ecosystems. Species that were not the object of studies on their biochemical composition include the Heterobranchia gastropods Armina maculata, Armina tigrina and Aglaja tricolorata, inhabitants of the Portuguese Atlantic coastal waters. Here, we present for the first time the fatty acid profile of neutral lipids and homarine content of these three species. Qualitative and quantitative differences in the fatty acid content among species points to the existence of a fatty acid profile of neutral lipids, particularly of each genus. The results from cytotoxicity assays, using the acetonic extracts of the gastropods on human gastric adenocarcinoma (AGS) and human lung adenocarcinoma (A549) cell lines, revealed a pronounced cytotoxic effect of the A. tigrina extract on both cell lines (IC50 values of 68.75 and 69.77 \u03bcg mL\u22121 for AGS and A549, respectively). It is worth noting the significant reduction of NO levels in LPS-challenged RAW 264.7 macrophages exposed to A. tricolorata extract, at concentrations as low as 125 \u03bcg mL\u22121.<\/jats:p>","DOI":"10.3390\/molecules23051027","type":"journal-article","created":{"date-parts":[[2018,4,27]],"date-time":"2018-04-27T05:35:08Z","timestamp":1524807308000},"page":"1027","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Profiling of Heterobranchia Sea Slugs from Portuguese Coastal Waters as Producers of Anti-Cancer and Anti-Inflammatory Agents"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8727-9678","authenticated-orcid":false,"given":"Nelson G. M.","family":"Gomes","sequence":"first","affiliation":[{"name":"REQUIMTE\/LAQV, Laboratory of Pharmacognosy, Departament of Chemistry, Faculty of Pharmacy, University of Porto, R. Jorge Viterbo Ferreira, no. 228, 4050-313 Porto, Portugal"}]},{"given":"F\u00e1tima","family":"Fernandes","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV, Laboratory of Pharmacognosy, Departament of Chemistry, Faculty of Pharmacy, University of Porto, R. Jorge Viterbo Ferreira, no. 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7569-6802","authenticated-orcid":false,"given":"\u00c1urea","family":"Madureira-Carvalho","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV, Laboratory of Pharmacognosy, Departament of Chemistry, Faculty of Pharmacy, University of Porto, R. Jorge Viterbo Ferreira, no. 228, 4050-313 Porto, Portugal"},{"name":"IINFACTS\u2014Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, University Institute of Health Sciences (IUCS), CESPU, CRL, Central de Gandra Street, 1317, 4585-116 Gandra PRD, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0740-4396","authenticated-orcid":false,"given":"Patr\u00edcia","family":"Valent\u00e3o","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV, Laboratory of Pharmacognosy, Departament of Chemistry, Faculty of Pharmacy, University of Porto, R. Jorge Viterbo Ferreira, no. 228, 4050-313 Porto, Portugal"}]},{"given":"Alexandre","family":"Lobo-da-Cunha","sequence":"additional","affiliation":[{"name":"Departamento de Microscopia, Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS), Universidade do Porto, 4050-313 Porto, Portugal"},{"name":"Centro Interdisciplinar de Investiga\u00e7\u00e3o Marinha e Ambiental (CIIMAR), 4450-208 Matosinhos, Portugal"}]},{"given":"Gon\u00e7alo","family":"Calado","sequence":"additional","affiliation":[{"name":"Departamento de Ci\u00eancias da Vida, Universidade Lus\u00f3fona de Humanidades e Tecnologia, 1749-024 Lisboa, Portugal"},{"name":"MARE NOVA. Faculdade de Ci\u00eancias e Tecnologia, Universidade Nova de Lisboa, Departamento de Ci\u00eancias e Engenharia do Ambiente, Campus da Caparica, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9764-3920","authenticated-orcid":false,"given":"Paula B.","family":"Andrade","sequence":"additional","affiliation":[{"name":"REQUIMTE\/LAQV, Laboratory of Pharmacognosy, Departament of Chemistry, Faculty of Pharmacy, University of Porto, R. Jorge Viterbo Ferreira, no. 228, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2018,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gomes, N.G.M., Dasari, R., Chandra, S., Kiss, R., and Kornienko, A. (2015). Marine invertebrate metabolites with anticancer activities: Solutions to the \u201csupply problem\u201d. Mar. Drugs, 98.","DOI":"10.3390\/md14050098"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Andrade, P.B., Valent\u00e3o, P., and Pereira, D.M. (2017). Targeting enzymatic pathways with marine-derived clinical agents. Natural Products Targeting Clinically Relevant Enzymes, Wiley-VCH Verlag GmbH & Co. KGaA.","DOI":"10.1002\/9783527805921"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1111\/j.1469-185X.2010.00124.x","article-title":"Molluscan biological and chemical diversity: Secondary metabolites and medicinal resources produced by marine molluscs","volume":"85","author":"Benkendorff","year":"2010","journal-title":"Biol. Rev. Camb. Philos. Soc."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Pereira, R.B., Andrade, P.B., and Valent\u00e3o, P. (2016). Chemical diversity and biological properties of secondary metabolites from sea hares of Aplysia genus. Mar. Drugs, 14.","DOI":"10.3390\/md14020039"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"202","DOI":"10.3390\/md13010202","article-title":"Statistical research on the bioactivity of new marine natural products discovered during the 28 years from 1985 to 2012","volume":"13","author":"Hu","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Leal, M.C., Puga, J., Ser\u00f4dio, J., Gomes, N.C.M., and Calado, R. (2012). Trends in the discovery of new marine natural products from invertebrates over the last two decades\u2014Where and what are we bioprospecting?. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0030580"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1017\/S0025315410002109","article-title":"Taxonomy and phylogeny of Armina (Gastropoda: Nudibranchia: Arminidae) from the Atlantic and eastern Pacific","volume":"91","author":"Ardila","year":"2011","journal-title":"J. Mar. Biol. Assoc. UK"},{"key":"ref_8","first-page":"1101","article-title":"Diet preferences of the Aglajidae: A family of cephalaspidean gastropod predators on tropical and temperate shores","volume":"96","author":"Malaquias","year":"2015","journal-title":"J. Mar. Biol. Assoc. UK"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.ympev.2013.11.010","article-title":"Phylogeny of the family Aglajidae (Pilsbry, 1895) (Heterobranchia: Cephalaspidea) inferred from mtDNA and nDNA","volume":"71","author":"Gosliner","year":"2014","journal-title":"Mol. Phylogenet. Evol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1017\/S0025315406013233","article-title":"Opisthobranch molluscs from the subtidal trawling grounds off Blanes (Girona, north-east Spain)","volume":"86","author":"Avila","year":"2006","journal-title":"J. Mar. Biol. Assoc. UK"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1002\/hlca.19900730206","article-title":"Isolation of the cembranoid preverecynarmin alongside some briaranes, the verecynarmins, from both the nudibranch mollusc Armina maculata and the octocoral Veretillum cynomorium of the east Pyrenean Mediterranean sea)","volume":"73","author":"Guerriero","year":"1990","journal-title":"Helv. Chim. Acta"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"108","DOI":"10.2174\/157341211795684781","article-title":"Fatty acids in marine organisms: In the pursuit of bioactive agents","volume":"7","author":"Pereira","year":"2011","journal-title":"Curr. Pharm. Anal."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.bse.2016.10.016","article-title":"3D chemoecology and chemotaxonomy of corals using fatty acid biomarkers: Latitude, longitude and depth","volume":"70","author":"Figueiredo","year":"2017","journal-title":"Biochem. Syst. Ecol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.bse.2016.03.016","article-title":"\u201cGone with the wind\u201d: Fatty acid biomarkers and chemotaxonomy of stranded pleustonic hydrozoans (Velella velella and Physalia physalis)","volume":"66","author":"Lopes","year":"2016","journal-title":"Biochem. Syst. Ecol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1016\/j.yexcr.2010.02.039","article-title":"Omega-3 fatty acids in cancer, the protectors of good and the killers of evil?","volume":"316","author":"Gleissman","year":"2010","journal-title":"Exp. Cell Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/bjc.2012.586","article-title":"Marine polyunsaturated fatty acids and cancer therapy","volume":"108","author":"Vaughan","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.bbalip.2014.08.010","article-title":"Marine omega-3 fatty acids and inflammatory processes: Effects, mechanisms and clinical relevance","volume":"1851","author":"Calder","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1039\/b923849m","article-title":"Defensive strategies of Cladobranchia (Gastropoda, Opisthobranchia)","volume":"27","author":"Putz","year":"2010","journal-title":"Nat. Prod. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.2174\/1381612043384637","article-title":"Biochemical aspects of nitric oxide","volume":"10","author":"Mariotto","year":"2004","journal-title":"Curr. Pharm. Des."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4578","DOI":"10.3390\/md12084578","article-title":"Lipids and fatty acids of nudibranch mollusks: Potential sources of bioactive compounds","volume":"12","author":"Zhukova","year":"2014","journal-title":"Mar. Drugs"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3998","DOI":"10.3390\/md11103998","article-title":"Biosynthesis of polyunsaturated fatty acids in marine invertebrates: Recent advances in molecular mechanisms","volume":"11","author":"Monroig","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"65","DOI":"10.3354\/meps08622","article-title":"Distribution of lipids and fatty acids in corals by their taxonomic position and presence of zooxanthellae","volume":"409","author":"Imbs","year":"2010","journal-title":"Mar. Ecol. Prog. Ser."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"508","DOI":"10.3906\/zoo-1309-26","article-title":"Armina maculata Rafinesque, 1814 (Nudibranchia: Arminidae): A new record for the Turkish mollusc fauna","volume":"38","author":"Akyol","year":"2014","journal-title":"Turk. J. Zool."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.cbpb.2011.11.002","article-title":"Temporal fatty acid dynamics of the octocoral Veretillum cynomorium","volume":"161","author":"Baptista","year":"2012","journal-title":"Comp. Biochem. Physiol. B Biochem. Mol. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.chemosphere.2017.02.031","article-title":"A comparative assessment of fatty acids in Antarctic organisms from the Ross Sea: Occurrence and distribution","volume":"174","author":"Corsolini","year":"2017","journal-title":"Chemosphere"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1007\/s11745-007-3123-8","article-title":"Lipid classes and fatty acid composition of the tropical nudibranch mollusks Chromodoris sp. and Phyllidia coelestis","volume":"42","author":"Zhukova","year":"2007","journal-title":"Lipids"},{"key":"ref_27","first-page":"181","article-title":"Distribution of homarine in some Opisthobranchia (Gastropoda: Mollusca)","volume":"55","author":"Affeld","year":"2007","journal-title":"Bonner Zool. Beitr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1080\/10575630108041311","article-title":"Homarine, a common metabolite in edible Mediterranean molluscs: Occurrence, spectral data and revision of a related structure","volume":"15","author":"Polychronopoulos","year":"2001","journal-title":"Nat. Prod. Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/1476-511X-12-71","article-title":"Effects of polyunsaturated fatty acids on the growth of gastric cancer cells in vitro","volume":"12","author":"Dai","year":"2013","journal-title":"Lipids Health Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.jada.2008.12.022","article-title":"A systemic review of the roles of n-3 fatty acids in health and disease","volume":"109","author":"Riediger","year":"2009","journal-title":"J. Am. Diet. Assoc."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"D\u2019Eliseo, D., and Velotti, F. (2016). Omega-3 fatty acids and cancer cell cytotoxicity: Implications for multi-targeted cancer therapy. J. Clin. Med., 5.","DOI":"10.3390\/jcm5020015"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2971","DOI":"10.3748\/wjg.v22.i10.2971","article-title":"Synergistic anticancer properties of docosahexaenoic acid and 5-fluorouracil through interference with energy metabolism and cell cycle arrest in human gastric cancer cell line AGS cells","volume":"22","author":"Gao","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Silva, T.C., de Andrade, P.B., Paiva-Martins, F., Valent\u00e3o, P., and Pereira, D.M. (2017). In vitro anti-inflammatory and cytotoxic effects of aqueous extracts from the edible sea anemones Anemonia sulcata and Actinia equina. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18030653"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2736","DOI":"10.3892\/ol.2015.3110","article-title":"Role of autophagy in the \u03c9-3 long chain polyunsaturated fatty acid-induced death of lung cancer A549 cells","volume":"9","author":"Yao","year":"2015","journal-title":"Oncol. Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.tiv.2015.09.013","article-title":"Toxic effects of n-3 polyunsaturated fatty acids in human lung A549 cells","volume":"30","author":"Zajdel","year":"2015","journal-title":"Toxicol. In Vitro"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.cbi.2006.12.014","article-title":"Arachidonic and docosahexaenoic acids reduce the growth of A549 human lung-tumor cells increasing lipid peroxidation and PPARs","volume":"165","author":"Trombetta","year":"2007","journal-title":"Chem. Biol. Interact."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"463","DOI":"10.2217\/clp.11.34","article-title":"Essential fatty acids enhance free radical generation and lipid peroxidation to induce apoptosis of tumor cells","volume":"6","author":"Das","year":"2011","journal-title":"Clin. Lipidol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.plipres.2007.12.004","article-title":"The opposing effects of n-3 and n-6 fatty acids","volume":"47","author":"Schmitz","year":"2008","journal-title":"Prog. Lipid Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.nut.2011.07.027","article-title":"Additive, antagonistic, and synergistic effects of procyanidins and polyunsaturated fatty acids over inflammation in RAW 264.7 macrophages activated by lipopolysaccharide","volume":"28","author":"Calay","year":"2012","journal-title":"Nutrition"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5073","DOI":"10.1021\/jf0702693","article-title":"Anti-inflammatory effect of \u03b1-linolenic acid and its mode of action through the inhibition of nitric oxide production and inducible nitric oxide synthase gene expression via NF-\u0138B and mitogen-activated protein kinase pathways","volume":"55","author":"Ren","year":"2007","journal-title":"J. Agric. Food Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s00394-009-0057-3","article-title":"Effect of polyunsaturated fatty acids on the reactive oxygen and nitrogen species production by raw 264.7 macrophages","volume":"49","author":"Ambrozova","year":"2010","journal-title":"Eur. J. Nutr."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.1038\/nprot.2008.182","article-title":"Methods for isolation, purification and structural elucidation of bioactive secondary metabolites from marine invertebrates","volume":"3","author":"Ebada","year":"2008","journal-title":"Nat. Protoc."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1021\/ac60171a016","article-title":"The rapid preparation of fatty acid esters for gas chromatographic analysis","volume":"33","author":"Metcalfe","year":"1961","journal-title":"Anal. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.jff.2017.07.053","article-title":"UHPLC-MS\/MS profiling of Aplysia depilans and assessment of its potential therapeutic use: Interference on iNOS expression in LPS-stimulated RAW 264.7 macrophages and caspase-mediated pro-apoptotic effect on SH-SY5Y cells","volume":"37","author":"Pereira","year":"2017","journal-title":"J. Funct. Foods"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.fct.2017.05.020","article-title":"Anti-inflammatory properties of the stem bark from the herbal drug Vitex peduncularis Wall. ex Schauer and characterization of its polyphenolic profile","volume":"106","author":"Ferreres","year":"2017","journal-title":"Food Chem. Toxicol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1021\/jf8031638","article-title":"Targeted metabolite analysis and biological activity of Pieris brassicae fed with Brassica rapa var. rapa","volume":"57","author":"Pereira","year":"2009","journal-title":"J. Agric. Food Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.tifs.2017.12.006","article-title":"Use of principal component analysis (PCA) and hierarchical cluster analysis (HCA) for multivariate association between bioactive compounds and functional properties in foods: A critical perspective","volume":"72","author":"Granato","year":"2018","journal-title":"Trends Food Sci. Technol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/23\/5\/1027\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:02:24Z","timestamp":1760194944000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/23\/5\/1027"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,27]]},"references-count":47,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2018,5]]}},"alternative-id":["molecules23051027"],"URL":"https:\/\/doi.org\/10.3390\/molecules23051027","relation":{},"ISSN":["1420-3049"],"issn-type":[{"type":"electronic","value":"1420-3049"}],"subject":[],"published":{"date-parts":[[2018,4,27]]}}}