{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T08:17:05Z","timestamp":1765268225985,"version":"build-2065373602"},"reference-count":25,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2013,12,24]],"date-time":"2013-12-24T00:00:00Z","timestamp":1387843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>We describe the effect of a chemically characterized lipophilic extract obtained from Marthasterias glacialis L. against human breast cancer (MCF-7) and human neuroblastoma (SH-SY5Y) cell lines. Evaluation of DNA synthesis revealed that both cell lines were markedly affected in a concentration-dependent way, the SH-SY5Y cell line being more susceptible. Cell cycle arrest was observed, an effect induced by the sterol, ergosta-7,22-dien-3-ol, present in the extract. Morphological evaluation of treated cells showed the advent of lipid droplets and chromatin condensation compatible with apoptosis, which was confirmed by the evaluation of caspase-3 and -9 activities. Palmitic acid was the main compound responsible for this apoptotic effect by a ceramide-independent mechanism that involved endoplasmic reticulum (ER)-stress with upregulation of CCAAT\/-enhancer-binding protein homologous protein (CHOP).<\/jats:p>","DOI":"10.3390\/md12010054","type":"journal-article","created":{"date-parts":[[2013,12,24]],"date-time":"2013-12-24T09:06:57Z","timestamp":1387876017000},"page":"54-68","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Palmitic Acid and Ergosta-7,22-dien-3-ol Contribute to the Apoptotic Effect and Cell Cycle Arrest of an Extract from Marthasterias glacialis L. in Neuroblastoma Cells"],"prefix":"10.3390","volume":"12","author":[{"given":"David","family":"Pereira","sequence":"first","affiliation":[{"name":"REQUIMTE\/Laboratory of Pharmacognosy, Department of Chemistry, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, n\u00ba 228, Porto 4050-313, Portugal"}]},{"given":"Georgina","family":"Correia-da-Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, n\u00ba 228, Porto 4050-313, Portugal"},{"name":"IBMC\u2014Instituto for Molecular and Cell Biology, University of Porto, Porto 4150-180, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0740-4396","authenticated-orcid":false,"given":"Patr\u00edcia","family":"Valent\u00e3o","sequence":"additional","affiliation":[{"name":"REQUIMTE\/Laboratory of Pharmacognosy, Department of Chemistry, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, n\u00ba 228, Porto 4050-313, Portugal"}]},{"given":"Nat\u00e9rcia","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, n\u00ba 228, Porto 4050-313, Portugal"},{"name":"IBMC\u2014Instituto for Molecular and Cell Biology, University of Porto, Porto 4150-180, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9764-3920","authenticated-orcid":false,"given":"Paula","family":"Andrade","sequence":"additional","affiliation":[{"name":"REQUIMTE\/Laboratory of Pharmacognosy, Department of Chemistry, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, n\u00ba 228, Porto 4050-313, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2013,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1039\/B515619J","article-title":"Anticancer drugs from nature\u2014natural products as a unique source of new microtubule-stabilizing agents","volume":"24","author":"Altmann","year":"2007","journal-title":"Nat. Prod. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/s11418-008-0246-z","article-title":"Plant-derived natural product research aimed at new drug discovery","volume":"62","author":"Itokawa","year":"2008","journal-title":"J. Nat. Med.-Tokyo"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"632","DOI":"10.2174\/138920112799857530","article-title":"Plant secondary metabolites in cancer chemotherapy: Where are we?","volume":"13","author":"Pereira","year":"2012","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.tips.2010.02.005","article-title":"The odyssey of marine pharmaceuticals: A current pipeline perspective","volume":"31","author":"Mayer","year":"2010","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.4155\/fmc.11.118","article-title":"Marine natural products: A new wave of drugs?","volume":"3","author":"Montaser","year":"2011","journal-title":"Future Med. Chem."},{"unstructured":"(2013). Studies in Natural Products Chemistry (Bioactive Natural Products), Elsevier Science Publishers.","key":"ref_6"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.biotechadv.2011.02.002","article-title":"Gold from the sea: marine compounds as inhibitors of the hallmarks of cancer","volume":"29","author":"Schumacher","year":"2011","journal-title":"Biotechnol. Adv."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.1002\/jssc.201000197","article-title":"HPLC-PAD-atmospheric pressure chemical ionization-MS metabolite profiling of cytotoxic carotenoids from the echinoderm Marthasterias glacialis (spiny sea-star)","volume":"33","author":"Ferreres","year":"2010","journal-title":"J. Sep. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.3390\/md10071498","article-title":"Further insights on the carotenoid profile of the echinoderm Marthasterias glacialis","volume":"10","author":"Mariutti","year":"2012","journal-title":"Mar. Drugs"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.talanta.2012.08.004","article-title":"A gas chromatography-mass spectrometry multi-target method for the simultaneous analysis of three classes of metabolites in marine organisms","volume":"100","author":"Pereira","year":"2012","journal-title":"Talanta"},{"unstructured":"Pereira, D.M., Correia-da-Silva, G., Valent\u00e3o, P., Mouga, T., Teixeira, N., and Andrade, P.B. (2013). A lipidomic approach to drug discovery from marine organisms: Effect of a purified fraction of the lipidome of the echinoderm Marthasterias glacialis L. against human cancer cells. Comb. Chem. High Throughput Screen., in press.","key":"ref_11"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/nrm2199","article-title":"Signal integration in the endoplasmic reticulum unfolded protein response","volume":"8","author":"Ron","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1146\/annurev.biochem.73.011303.074134","article-title":"The mammalian unfolded protein response","volume":"74","author":"Schroder","year":"2005","journal-title":"Annu. Rev. Biochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/nature07203","article-title":"From endoplasmic-reticulum stress to the inflammatory response","volume":"454","author":"Zhang","year":"2008","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"H717","DOI":"10.1152\/ajpheart.00257.2001","article-title":"Palmitate-induced cardiac apoptosis is mediated through CPT-1 but not influenced by glucose and insulin","volume":"282","author":"Kong","year":"2002","journal-title":"Am. J. Physiol.-Heart Circ. 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Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/S0006-291X(02)02593-7","article-title":"Ceramide induces neuronal apoptosis through the caspase-9\/caspase-3 pathway","volume":"299","author":"Movsesyan","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.neuroscience.2010.11.035","article-title":"Palmitate induces apoptosis in Schwann cells via both ceramide-dependent and independent pathways","volume":"176","author":"Suzuki","year":"2011","journal-title":"Neuroscience"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1210\/er.2007-0025","article-title":"Sphingolipids, insulin resistance, and metabolic disease: New insights from in vivo manipulation of sphingolipid metabolism","volume":"29","author":"Holland","year":"2008","journal-title":"Endocr. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"E275","DOI":"10.1152\/ajpendo.00644.2005","article-title":"Saturated fatty acids induce endoplasmic reticulum stress and apoptosis independently of ceramide in liver cells","volume":"291","author":"Wei","year":"2006","journal-title":"Am. J. Physiol.-Endocrinol. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e55537","DOI":"10.1371\/journal.pone.0055537","article-title":"Membrane lipidome reorganization correlates with the fate of neuroblastoma cells supplemented with fatty acids","volume":"8","author":"Bolognesi","year":"2013","journal-title":"PLoS One"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/nature02451","article-title":"Differential modulation of endotoxin responsiveness by human caspase-12 polymorphisms","volume":"429","author":"Saleh","year":"2004","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1111\/j.1744-313X.2012.01107.x","article-title":"Presence of the functional CASPASE-12 allele in Indian subpopulations","volume":"39","author":"Yavari","year":"2012","journal-title":"Int. J. 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