{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T23:37:28Z","timestamp":1790206648889,"version":"4.1.0"},"reference-count":37,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2019,10,16]],"date-time":"2019-10-16T00:00:00Z","timestamp":1571184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["2890\/33528"],"award-info":[{"award-number":["2890\/33528"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Conseil R\u00e9gional de Basse-Normandie","award":["12PO1493"],"award-info":[{"award-number":["12PO1493"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>The purpose of the present paper is to investigate the mechanism of action of a pyroglutamate-modified peptide (pE-K092D) on in vitro growth inhibition of MDA-Pca-2b prostate cancer cells. This peptide was derived from a peptide previously isolated from the testis of the lesser spotted dogfish and identified as QLTPEALADEEEMNALAAR (K092D). The effect of the peptide on cell proliferation and cell death mechanisms was studied by flow cytometry. Cellular morphology and cytoskeleton integrity of peptide-treated cells were observed by immunofluorescence microscopy. Results showed the onset of peptide induced early cytoskeleton perturbation, inhibition of autophagy, inhibition of cell proliferation and, at the end, non-apoptotic cell death mechanisms (membrane destabilization and necrosis). All those mechanisms seem to contribute to MDA-Pca-2b growth inhibition by a main cytostatic fate.<\/jats:p>","DOI":"10.3390\/md17100585","type":"journal-article","created":{"date-parts":[[2019,10,17]],"date-time":"2019-10-17T04:46:06Z","timestamp":1571287566000},"page":"585","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Potential Antineoplastic Peptide of Human Prostate Cancer Cells Derived from the Lesser Spotted Dogfish (Scyliorhinus canicula L.)"],"prefix":"10.3390","volume":"17","author":[{"given":"Adrien","family":"Bosseboeuf","sequence":"first","affiliation":[{"name":"Sciences Department, Normandy University, University of Caen Normandy (UNICAEN), Sorbonne University, French National Museum of Natural History (MNHN), University of Antilles (UA), French National Centre for Scientific Research (CNRS), French National Institute for Sustainable Development (IRD), Biology of Aquatic Organisms and Ecosystems (BOREA) Research Unit, CS14032, 14032 CAEN, CEDEX 5, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amandine","family":"Baron","sequence":"additional","affiliation":[{"name":"Group CELLIS PHARMA, Parc Technopolitain Atalante Saint Malo, 35400 Saint Malo, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise","family":"Duval","sequence":"additional","affiliation":[{"name":"Group CELLIS PHARMA, Parc Technopolitain Atalante Saint Malo, 35400 Saint Malo, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aude","family":"Gautier","sequence":"additional","affiliation":[{"name":"Sciences Department, Normandy University, University of Caen Normandy (UNICAEN), Sorbonne University, French National Museum of Natural History (MNHN), University of Antilles (UA), French National Centre for Scientific Research (CNRS), French National Institute for Sustainable Development (IRD), Biology of Aquatic Organisms and Ecosystems (BOREA) Research Unit, CS14032, 14032 CAEN, CEDEX 5, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Sourdaine","sequence":"additional","affiliation":[{"name":"Sciences Department, Normandy University, University of Caen Normandy (UNICAEN), Sorbonne University, French National Museum of Natural History (MNHN), University of Antilles (UA), French National Centre for Scientific Research (CNRS), French National Institute for Sustainable Development (IRD), Biology of Aquatic Organisms and Ecosystems (BOREA) Research Unit, CS14032, 14032 CAEN, CEDEX 5, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierrick","family":"Auvray","sequence":"additional","affiliation":[{"name":"Group CELLIS PHARMA, Parc Technopolitain Atalante Saint Malo, 35400 Saint Malo, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"963","DOI":"10.3390\/md10050963","article-title":"Bioactive peptides and depsipeptides with anticancer potential: Sources from marine animals","volume":"10","year":"2012","journal-title":"Mar. Drugs"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"885","DOI":"10.2174\/1389203717666160724200849","article-title":"Marine Peptides as Anticancer Agents: A Remedy to Mankind by Nature","volume":"18","author":"Negi","year":"2017","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.peptides.2017.06.002","article-title":"Structural diversity of marine cyclic peptides and their molecular mechanisms for anticancer, antibacterial, antifungal, and other clinical applications","volume":"95","author":"Lee","year":"2017","journal-title":"Peptides"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1002\/pro.2927","article-title":"From amino acid sequence to bioactivity: The biomedical potential of antitumor peptides","volume":"25","year":"2016","journal-title":"Protein Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"637","DOI":"10.3892\/or.2017.5778","article-title":"Anticancer potential of bioactive peptides from animal sources (Review)","volume":"38","author":"Wang","year":"2017","journal-title":"Oncol. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"160","DOI":"10.3390\/md16050160","article-title":"Investigation of the Anti-Prostate Cancer Properties of Marine-Derived Compounds","volume":"16","author":"Fan","year":"2018","journal-title":"Mar. Drugs"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.3390\/md10102153","article-title":"Sepia ink oligopeptide induces apoptosis in prostate cancer cell lines via caspase-3 activation and elevation of Bax\/Bcl-2 ratio","volume":"10","author":"Huang","year":"2012","journal-title":"Mar. Drugs"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4222","DOI":"10.3892\/mmr.2017.7068","article-title":"Isolation and purification of novel peptides derived from Sepia ink: Effects on apoptosis of prostate cancer cell PC-3","volume":"16","author":"Huang","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6697","DOI":"10.3892\/mmr.2017.7418","article-title":"Two novel peptides derived from Sinonovacula constricta inhibit the proliferation and induce apoptosis of human prostate cancer cells","volume":"16","author":"Huang","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_10","first-page":"771","article-title":"A novel anti-proliferative pentapeptide (ILYMP) isolated from Cyclina sinensis protein hydrolysate induces apoptosis of DU-145 prostate cancer cells","volume":"18","author":"Yu","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_11","first-page":"3912","article-title":"A Phase I and Pharmacokinetic Study of Squalamine, a Novel Antiangiogenic Agent, in Patients with Advanced Cancers","volume":"7","author":"Bhargava","year":"2001","journal-title":"Clin. Cancer Res."},{"key":"ref_12","first-page":"381","article-title":"Squalamine lactate for exudative age-related macular degeneration","volume":"19","author":"Connolly","year":"2006","journal-title":"Ophthalmol. Clin. N. Am."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"15978","DOI":"10.1073\/pnas.1108558108","article-title":"Squalamine as a broad-spectrum systemic antiviral agent with therapeutic potential","volume":"108","author":"Zasloff","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.canlet.2019.02.009","article-title":"Squalamine blocks tumor-associated angiogenesis and growth of human breast cancer cells with or without HER-2\/neu overexpression","volume":"449","author":"Chen","year":"2019","journal-title":"Cancer Lett."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"258","DOI":"10.3390\/md7020258","article-title":"Expression, purification and bioactivities analysis of recombinant active peptide from shark liver","volume":"7","author":"Lv","year":"2009","journal-title":"Mar. Drugs"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1046\/j.1444-2906.2002.00518.x","article-title":"Purification of angiotensin I-converting enzyme inhibitors in pelagic thresher Alopias pelagicus muscle hydrolysate and viscera extracts","volume":"68","author":"Nomura","year":"2002","journal-title":"Fish Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.jff.2015.06.062","article-title":"Production and identification of angiotensin I-converting enzyme (ACE) inhibitory peptides from Mediterranean fish discards","volume":"18","author":"Guadix","year":"2015","journal-title":"J. Funct. Foods"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.foodchem.2014.11.013","article-title":"Angiotensin-I converting enzyme inhibitory peptides from antihypertensive skate (Okamejei kenojei) skin gelatin hydrolysate in spontaneously hypertensive rats","volume":"174","author":"Ngo","year":"2015","journal-title":"Food Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"775","DOI":"10.4161\/cbt.6.5.4002","article-title":"A novel polypeptide from shark cartilage with potent anti-angiogenic activity","volume":"6","author":"Zheng","year":"2007","journal-title":"Cancer Biol. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Pan, X., Zhao, Y.Q., Hu, F.Y., Chi, C.F., and Wang, B. (2016). Anticancer Activity of a Hexapeptide from Skate (Raja porosa) Cartilage Protein Hydrolysate in HeLa Cells. Mar. Drugs, 14.","DOI":"10.3390\/md14080153"},{"key":"ref_21","unstructured":"Auvray, P., and Duval, E. (2012). Peptides isol\u00e9s et purifi\u00e9s \u00e0 partir de testicules de roussettes. WO 2012\/130999 A1."},{"key":"ref_22","first-page":"362","article-title":"Autophagy regulation in cancer development and therapy","volume":"1","author":"White","year":"2011","journal-title":"Am. J. Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"232","DOI":"10.4331\/wjbc.v2.i10.232","article-title":"Mechanisms of autophagy and apoptosis: Recent developments in breast cancer cells","volume":"2","author":"Esteve","year":"2011","journal-title":"World J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s12943-015-0321-5","article-title":"Apoptosis, autophagy, necroptosis, and cancer metastasis","volume":"14","author":"Su","year":"2015","journal-title":"Mol. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.3892\/ijo.2014.2659","article-title":"Viriditoxin regulates apoptosis and autophagy via mitotic catastrophe and microtubule formation in human prostate cancer cells","volume":"45","author":"Kundu","year":"2014","journal-title":"Int. J. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s00280-015-2915-4","article-title":"Malformin A1 promotes cell death through induction of apoptosis, necrosis and autophagy in prostate cancer cells","volume":"77","author":"Liu","year":"2016","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1172\/JCI28833","article-title":"Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma","volume":"117","author":"Amaravadi","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Racoma, I.O., Meisen, W.H., Wang, Q.-E., Kaur, B., and Wani, A.A. (2013). Thymoquinone inhibits autophagy and induces cathepsin-mediated, caspase-independent cell death in glioblastoma cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0072882"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"R318","DOI":"10.1016\/j.cub.2017.02.061","article-title":"The Cytoskeleton-Autophagy Connection","volume":"27","author":"Kast","year":"2017","journal-title":"Curr. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Wills, J., Credle, J., Oaks, A.W., Duka, V., Lee, J.-H., Jones, J., and Sidhu, A. (2012). Paraquat, but not maneb, induces synucleinopathy and tauopathy in striata of mice through inhibition of proteasomal and autophagic pathways. PLoS ONE, 7.","DOI":"10.1371\/annotation\/6c09a04c-e565-4a34-b24e-90f084463e15"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.15252\/embr.201642292","article-title":"Regulation of mitotic spindle orientation: An integrated view","volume":"17","author":"Echard","year":"2016","journal-title":"EMBO Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1093\/carcin\/bgg192","article-title":"Sulforaphane: A naturally occurring mammary carcinoma mitotic inhibitor, which disrupts tubulin polymerization","volume":"25","author":"Jackson","year":"2004","journal-title":"Carcinogenesis"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3360","DOI":"10.1158\/1535-7163.MCT-09-0798","article-title":"Antimitotic effect of the retinoid 4-oxo-fenretinide through inhibition of tubulin polymerization: A novel mechanism of retinoid growth-inhibitory activity","volume":"8","author":"Appierto","year":"2009","journal-title":"Mol. Cancer Ther."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Duangmano, S., Sae-Lim, P., Suksamrarn, A., Domann, F.E., and Patmasiriwat, P. (2012). Cucurbitacin B inhibits human breast cancer cell proliferation through disruption of microtubule polymerization and nucleophosmin\/B23 translocation. BMC Complement. Altern. Med., 12.","DOI":"10.1186\/1472-6882-12-185"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1093\/genetics\/163.1.21","article-title":"Loss of CDC5 Function in Saccharomyces cerevisiae Leads to Defects in Swe1p Regulation and Bfa1p\/Bub2p-Independent Cytokinesis","volume":"33","author":"Park","year":"2003","journal-title":"Genetics"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.bbamcr.2011.01.004","article-title":"Cytoskeletal remodeling by C3G to induce neurite-like extensions and inhibit motility in highly invasive breast carcinoma cells","volume":"1813","author":"Dayma","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7043","DOI":"10.1016\/j.biomaterials.2010.05.023","article-title":"Actions of the anti-cancer drug suberoylanilide hydroxamic acid (SAHA) on human breast cancer cytoarchitecture in silicon microstructures","volume":"31","author":"Strobl","year":"2010","journal-title":"Biomaterials"}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/17\/10\/585\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:26:55Z","timestamp":1760189215000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/17\/10\/585"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,16]]},"references-count":37,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2019,10]]}},"alternative-id":["md17100585"],"URL":"https:\/\/doi.org\/10.3390\/md17100585","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,16]]}}}