{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:30:54Z","timestamp":1791307854186,"version":"4.3.1"},"reference-count":60,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2015,6,3]],"date-time":"2015-06-03T00:00:00Z","timestamp":1433289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>The venom from the ectoparasitoid wasp Nasonia vitripennis (Hymenoptera: Pteromalidae) contains at least 80 different proteins and possibly even more peptides or other small chemical compounds, demonstrating its appealing therapeutic application. To better understand the dynamics of the venom in mammalian cells, two high-throughput screening tools were performed. The venom induced pathways related to an early stress response and activated reporters that suggest the involvement of steroids. Whether these steroids reside from the venom itself or show an induced release\/production caused by the venom, still remains unsolved. The proinflammatory cytokine IL-1\u03b2 was found to be down-regulated after venom and LPS co-treatment, confirming the anti-inflammatory action of N. vitripennis venom. When analyzing the expression levels of the NF-\u03baB target genes, potentially not only the canonical but also the alternative NF-\u03baB pathway can be affected, possibly explaining some counterintuitive results. It is proposed that next to an NF-\u03baB binding site, the promoter of the genes tested by the PCR array may also contain binding sites for other transcription factors, resulting in a complex puzzle to connect the induced target gene with its respective transcription factor. Interestingly, Nasonia venom altered the expression of some drug targets, presenting the venom with an exciting therapeutical potential.<\/jats:p>","DOI":"10.3390\/toxins7062051","type":"journal-article","created":{"date-parts":[[2015,6,3]],"date-time":"2015-06-03T11:29:39Z","timestamp":1433330979000},"page":"2051-2070","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Exploring the Potential of Venom from Nasonia vitripennis as Therapeutic Agent with High-Throughput Screening Tools"],"prefix":"10.3390","volume":"7","author":[{"given":"Ellen","family":"Danneels","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Entomology and Bee Pathology, Ghent University, S2 Krijgslaan 281,  B-9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Formesyn","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Entomology and Bee Pathology, Ghent University, S2 Krijgslaan 281,  B-9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8817-0781","authenticated-orcid":false,"given":"Dirk","family":"De Graaf","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Entomology and Bee Pathology, Ghent University, S2 Krijgslaan 281,  B-9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/j.1365-2583.2009.00914.x","article-title":"Insights into the venom composition of the ectoparasitoid wasp Nasonia vitripennis from bioinformatic and proteomic studies","volume":"19","author":"Aerts","year":"2010","journal-title":"Insect Mol. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.toxicon.2010.03.024","article-title":"A defensin antimicrobial peptide from the venoms of Nasonia vitripennis","volume":"56","author":"Ye","year":"2010","journal-title":"Toxicon"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1126\/science.1116364","article-title":"The renaissance of natural products as drug candidates","volume":"310","author":"Paterson","year":"2005","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4769","DOI":"10.1016\/j.ejmech.2011.07.057","article-title":"Natural products: An evolving role in future drug discovery","volume":"46","author":"Mishra","year":"2011","journal-title":"Eur. J. Med. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1146\/annurev.genom.9.081307.164356","article-title":"The toxicogenomic multiverse: Convergent recruitment of proteins into animal venoms","volume":"10","author":"Fry","year":"2009","journal-title":"Annu. Rev. Genomics Hum. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/S2221-1691(13)60042-8","article-title":"Therapeutic potential of snake venom in cancer therapy: Current perspectives","volume":"3","author":"Vyas","year":"2013","journal-title":"Asian Pac. J. Trop. Biomed."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.pharmthera.2007.04.004","article-title":"Therapeutic application of anti-arthritis, pain-releasing, and anti-cancer effects of bee venom and its constituent compounds","volume":"115","author":"Son","year":"2007","journal-title":"Pharmacol. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e96825","DOI":"10.1371\/journal.pone.0096825","article-title":"How the venom from the ectoparasitoid wasp Nasonia vitripennis exhibits anti-inflammatory properties on mammalian cell lines","volume":"9","author":"Danneels","year":"2014","journal-title":"PLoS ONE"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1016\/j.dci.2005.11.001","article-title":"A calreticulin-like protein from endoparasitoid venom fluid is involved in host hemocyte inactivation","volume":"30","author":"Zhang","year":"2006","journal-title":"Dev. Comp. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9427","DOI":"10.1073\/pnas.1222351110","article-title":"Parasitoid wasp venom SERCA regulates Drosophila calcium levels and inhibits cellular immunity","volume":"110","author":"Mortimer","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","first-page":"124","article-title":"Drugs from bugs, Part 1: The \u201cnew\u201d alternative medicine for the 21st century?","volume":"15","author":"Cherniack","year":"2010","journal-title":"Altern. Med. Ref."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1146\/annurev.immunol.021908.132641","article-title":"Regulation and function of NF-\u03baB transcription factors in the immune system","volume":"27","author":"Vallabhapurapu","year":"2009","journal-title":"Annu. Rev. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1124\/mi.2.1.22","article-title":"Inhibition of nuclear factor \u03baB (NF-B): An emerging theme in anti-inflammatory therapies","volume":"2","author":"May","year":"2002","journal-title":"Mol. Interv."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1007\/s00018-013-1545-4","article-title":"NF-\u03baB pathways in hematological malignancies","volume":"71","author":"Gasparini","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6853","DOI":"10.1038\/sj.onc.1203239","article-title":"Activators and target genes of Rel\/NF-\u03baB transcription factors","volume":"18","author":"Pahl","year":"1999","journal-title":"Oncogene"},{"key":"ref_16","unstructured":"NF-\u03baB Transcription Factors. Available online: http:\/\/www.bu.edu\/nf-kb\/gene-resources\/target-genes\/."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1007\/s00109-007-0227-9","article-title":"Many faces of NF-\u03baB signaling induced by genotoxic stress","volume":"85","author":"Wu","year":"2007","journal-title":"J. Mol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1007\/s11255-015-0954-8","article-title":"Augmenter of liver regeneration attenuates inflammation of renal ischemia\/reperfusion injury throuth the NF-\u03baB pathway in rats","volume":"47","author":"Yan","year":"2015","journal-title":"Int. Urol. Nephrol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1111\/bph.12224","article-title":"Activation of NF-\u03baB after chronic ethanol intake and haemorrhagic shock\/resuscitation in mice","volume":"170","author":"Maraslioglu","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1111\/j.1365-2796.2011.02353.x","article-title":"Cardiovascular disease associated with radiotherapy: Activation of nuclear factor kappa-B","volume":"269","author":"Halle","year":"2011","journal-title":"J. Intern. Med."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Samuel, T., Fadlalla, K., Gales, D.N., Putcha, B.D.K., and Manne, U. (2014). Variable NF-\u03baB pathway responses in colon cancer cells treated with chemotherapeutic drugs. BMC Cancer, 14.","DOI":"10.1186\/1471-2407-14-599"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3828","DOI":"10.1046\/j.1432-1327.2000.01421.x","article-title":"The pro- or anti-apoptotic function of NF-kappa B is determined by the nature of the apoptotic stimulus","volume":"267","author":"Kaltschmidt","year":"2000","journal-title":"Eur. J. Biochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e6992","DOI":"10.1371\/journal.pone.0006992","article-title":"Addressing reported pro-apoptotic functions of NF-\u03baB: Targeted inhibition of canonical NF-\u03baB enhances the apoptotic effects of doxorubicin","volume":"4","author":"Bednarski","year":"2009","journal-title":"PLoS ONE"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1146\/annurev.nutr.24.012003.132145","article-title":"Nutritional control of gene expression: How mammalian cells respond to amino acid limitation","volume":"25","author":"Kilberg","year":"2005","journal-title":"Annu. Rev. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6515","DOI":"10.1128\/MCB.00489-09","article-title":"Identification of a novel amino acid response pathway triggering ATF2 phosphorylation in mammals","volume":"29","author":"Chaveroux","year":"2009","journal-title":"Mol. Cell. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1111\/jcmm.12409","article-title":"Di(2-ethylhexyl) phthalate-induced apoptosis in rat INS-1 cells is dependent on activation of endoplasmic reticulum stress and suppression of antioxidant protection","volume":"19","author":"Sun","year":"2015","journal-title":"J. Cell. Mol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1007\/s11306-014-0697-z","article-title":"Parasitoid venom induces metabolic cascades in fly hosts","volume":"11","author":"Mrinalini","year":"2015","journal-title":"Metabolomics"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Ronci, M., Catanzaro, G., Pieroni, L., Po, A., Besherat, Z.M., Greco, V., Mortera, S.L., Screpanti, I., Ferretti, E., and Urbani, A. (2015). Proteomic analysis of human sonic hedgehog (SHH) medulloblastoma stem-like cells. Mol. BioSyst.","DOI":"10.1039\/C5MB00034C"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1016\/j.ibmb.2013.10.003","article-title":"Early changes in the pupal transcriptome of the flesh fly Sarcophagha crassipalpis to parasitization by the ectoparasitic wasp, Nasonia vitripennis","volume":"43","author":"Danneels","year":"2013","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"494","DOI":"10.3390\/toxins2040494","article-title":"Venom proteins of the parasitoid wasp Nasonia vitripennis: Recent discovery of an untapped pharmacopee","volume":"2","author":"Danneels","year":"2010","journal-title":"Toxins"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5899","DOI":"10.1073\/pnas.0510996103","article-title":"Coordinated binding of NF-kappaB family members in the response of human cells to lipopolysaccharide","volume":"103","author":"Schreiber","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/S0891-5849(00)00300-2","article-title":"Persuasive evidence that quinone reductase type 1 (DT diaphorase) protects cells against the toxicity of electrophiles and reactive forms of oxygen","volume":"29","author":"Talalay","year":"2000","journal-title":"Free Radic. Biol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.ibmb.2007.02.005","article-title":"A gamma-glutamyl transpeptidase of Aphidius ervi venom induces apoptosis in the ovaries of host aphids","volume":"37","author":"Falabella","year":"2007","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1111\/jpi.12123","article-title":"Melatonin alleviates Echis carinatus venom-induced toxicities by modulating inflammatory mediators and oxidative stress","volume":"56","author":"Katkar","year":"2014","journal-title":"J. Pineal Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1111\/j.1440-1827.1996.tb03641.x","article-title":"Development and heterogeneity of macrophages and their related cells through their differentiation pathways","volume":"46","author":"Takahashi","year":"1996","journal-title":"Pathol. Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1146\/annurev.immunol.18.1.621","article-title":"Phosphorylation meets ubiquitination: The control of NF-\u03baB activity","volume":"18","author":"Karin","year":"2000","journal-title":"Annu. Rev. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/S1097-2765(01)00187-3","article-title":"NF-\u03baB-inducing kinase regulates the processing of NF-\u03baB2 p100","volume":"7","author":"Xiao","year":"2001","journal-title":"Mol. Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/sj.embor.embor710","article-title":"Lymphotoxin and lipopolysaccharide induce NF-kappaB-p52 generation by a co-translational mechanism","volume":"4","author":"Mordmuller","year":"2003","journal-title":"EMBO Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4202","DOI":"10.1038\/sj.emboj.7600391","article-title":"Activation of IKK alpha target genes depends on recognition of specific kappa B binding sites by RelB:p52 dimers","volume":"23","author":"Bonizzi","year":"2004","journal-title":"EMBO J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.jinsphys.2013.05.004","article-title":"The role of serine- and metalloproteases in Nasonia vitripennis venom in cell death related processes towards a Spodoptera frugiperda Sf21 cell line","volume":"59","author":"Formesyn","year":"2013","journal-title":"J. Insect Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"14871","DOI":"10.1073\/pnas.96.26.14871","article-title":"Activation of Fas by FasL induces apoptosis by a mechanism that cannot be blocked by Bcl-2 or Bcl-x(L)","volume":"96","author":"Huang","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e43436","DOI":"10.1371\/journal.pone.0043436","article-title":"Gene network revealed involvements of Birc2, Birc3 and Tnfrsf1a in anti-apoptosis of injured peripheral nerves","volume":"7","author":"Wang","year":"2012","journal-title":"PLoS ONE"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5849","DOI":"10.1128\/MCB.23.16.5849-5856.2003","article-title":"TRAF2 exerts its antiapoptotic effect by regulating the expression of Kruppel-like factor LKLF","volume":"23","author":"Lin","year":"2003","journal-title":"Mol. Cell. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1084\/jem.193.12.1351","article-title":"Two waves of nuclear factor kappa B recruitment to target promoters","volume":"193","author":"Saccani","year":"2001","journal-title":"J. Exp. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1158\/1541-7786.MCR-11-0072","article-title":"C\/EBPalpha, C\/EBPalpha oncoproteins, or C\/EBPbeta preferentially bind NF-\u03baB p50 compared with p65, focusing therapeutic targeting on the C\/EBP:p50 interaction","volume":"9","author":"Dooher","year":"2011","journal-title":"Mol. Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1042\/BST0361224","article-title":"How do microRNAs regulate gene expression?","volume":"36","author":"Cannell","year":"2008","journal-title":"Biochem. Soc. Trans."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"S245","DOI":"10.1038\/ng1089","article-title":"Epigenetic regulation of gene expression: How the genome integrates intrinsic and environmental signals","volume":"33","author":"Jaenisch","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1093\/annonc\/mds351","article-title":"Epidermal growth factor receptor (EGFR) inhibitors and derived treatments","volume":"23","author":"Dziadziuszko","year":"2012","journal-title":"Ann. Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"11398","DOI":"10.1073\/pnas.0404328101","article-title":"Critical role for granulocyte colony-stimulating factor in inflammatory arthritis","volume":"101","author":"Lawlor","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/0002-9343(94)90326-3","article-title":"Interferon-gamma and host antimicrobial defense\u2014Current and future clinical-applications","volume":"97","author":"Murray","year":"1994","journal-title":"Am. J. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1093\/carcin\/bgi113","article-title":"Interferon regulatory factor-1 (IRF-1) exhibits tumor suppressor activities in breast cancer associated with caspase activation and induction of apoptosis","volume":"26","author":"Bouker","year":"2005","journal-title":"Carcinogenesis"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1182\/blood.V97.5.1422","article-title":"Low NAD(P)H: Quinone oxidoreductase 1 activity is associated with increased risk of acute leukemia in adults","volume":"97","author":"Smith","year":"2001","journal-title":"Blood"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s10549-005-9066-y","article-title":"Validation of cyclin D1\/CDK4 as an anticancer drug target in MCF-7 breast cancer cells: Effect of regulated overexpression of cyclin D1 and siRNA-mediated inhibition of endogenous cyclin D1 and CDK4 expression","volume":"95","author":"Grillo","year":"2006","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3853","DOI":"10.1007\/s00018-011-0763-x","article-title":"Matrix metalloproteinases in tumorigenesis: An evolving paradigm","volume":"68","author":"Hua","year":"2011","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/j.cell.2010.02.043","article-title":"Anti-inflammatory agents: Present and future","volume":"140","author":"Dinarello","year":"2010","journal-title":"Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"6042","DOI":"10.1021\/jm900781m","article-title":"Structure-activity relationships for substrate-based inhibitors of human complement factor B","volume":"52","author":"Lim","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Ellrichmann, G., Thone, J., Lee, D.H., Rupec, R.A., Gold, R., and Linker, R.A. (2012). Constitutive activity of NF-\u03baB in myeloid cells drives pathogenicity of monocytes and macrophages during autoimmune neuroinflammation. J. Neuroinflamm., 9.","DOI":"10.1186\/1742-2094-9-15"},{"key":"ref_58","first-page":"518","article-title":"Constitutive NF-kappaB activity in colorectal cancer cells: Impact on radiation-induced NF-\u03baB activity, radiosensitivity, and apoptosis","volume":"53","author":"Voboril","year":"2006","journal-title":"Neoplasma"},{"key":"ref_59","unstructured":"Beckage, N.E., and Drezen, J. (2013). Parasitoid Viruses: Symbionts and Pathogens, Academic Press, Elsevier. [19th ed.]."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"15827","DOI":"10.1073\/pnas.0505554102","article-title":"A fully dissociated compound of plant origin for inflammatory gene repression","volume":"102","author":"Beck","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/7\/6\/2051\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T20:47:23Z","timestamp":1760215643000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/7\/6\/2051"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,3]]},"references-count":60,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2015,6]]}},"alternative-id":["toxins7062051"],"URL":"https:\/\/doi.org\/10.3390\/toxins7062051","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,6,3]]}}}