{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:34:54Z","timestamp":1760142894256,"version":"build-2065373602"},"reference-count":50,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T00:00:00Z","timestamp":1704931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Marine Biodiversity Institute of Korea"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>This study aims to explore the potential inhibition effects of staurosporine isolated from a Streptomyces sp. SNC087 strain obtained from seawater on nasal polyps. Staurosporine possesses antimicrobial and antihypertensive activities. This research focuses on investigating the effects of staurosporine on suppressing the growth and development of nasal polyps and elucidating the underlying mechanisms involved. The experimental design includes in vitro and ex vivo evaluations to assess the inhibition activity and therapeutic potential of staurosporine against nasal polyps. Nasal polyp-derived fibroblasts (NPDFs) were stimulated with TGF-\u03b21 in the presence of staurosporine. The levels of \u03b1-smooth muscle actin (\u03b1-SMA), collagen type-I (Col-1), fibronectin, and phosphorylated (p)-Smad 2 were investigated using Western blotting. VEGF expression levels were analyzed in nasal polyp organ cultures treated with staurosporine. TGF-\u03b21 stimulated the production of Col-1, fibronectin, and \u03b1-SMA and was attenuated by staurosporine pretreatment. Furthermore, these inhibitory effects were mediated by modulation of the signaling pathway of Smad 2 in TGF-\u03b21-induced NPDFs. Staurosporine also inhibits the production of VEGF in ex vivo NP tissues. The findings from this study will contribute to a better understanding of staurosporine\u2019s role in nasal polyp management and provide insights into its mechanisms of action.<\/jats:p>","DOI":"10.3390\/md22010039","type":"journal-article","created":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T05:24:12Z","timestamp":1704950652000},"page":"39","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Inhibition Effect and Mechanism of Staurosporine Isolated from Streptomyces sp. SNC087 Strain on Nasal Polyp"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8009-8006","authenticated-orcid":false,"given":"Grace","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Microbial Resources, National Marine Biodiversity Institute of Korea, Seocheon 33662, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun-Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Nanoscience, Ewha Womans University, Seoul 03760, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0542-6866","authenticated-orcid":false,"given":"Dawoon","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Microbial Resources, National Marine Biodiversity Institute of Korea, Seocheon 33662, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kichul","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Microbial Resources, National Marine Biodiversity Institute of Korea, Seocheon 33662, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Woon-Jong","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Microbial Resources, National Marine Biodiversity Institute of Korea, Seocheon 33662, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0944-6565","authenticated-orcid":false,"given":"Sang-Jip","family":"Nam","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Nanoscience, Ewha Womans University, Seoul 03760, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seong-Kook","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head & Neck Surgery, Busan Paik Hospital, Inje University College of Medicine, Busan 47392, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3958-6937","authenticated-orcid":false,"given":"Il-Whan","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Inje University College of Medicine, Busan 47392, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"507","DOI":"10.2147\/TCRM.S2379","article-title":"A review of nasal polyposis","volume":"4","author":"Jonathan","year":"2008","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"8061","DOI":"10.1038\/s41598-019-44627-z","article-title":"Eosinophil extracellular trap formation is closely associated with disease severity in chronic rhinosinusitis regardless of nasal polyp status","volume":"9","author":"Hwang","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1016\/j.jaci.2014.03.022","article-title":"Biology of nasal polyposis","volume":"133","author":"Stevens","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S733","DOI":"10.1007\/s12070-022-03247-2","article-title":"Pathogenesis of Nasal Polyposis: Current Trends","volume":"75","author":"Goulioumis","year":"2023","journal-title":"Indian J. Otolaryngol. Head Neck Surg."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Rizzi, A., Gammeri, L., Cordiano, R., Valentini, M., Centrone, M., Marrone, S., Inchingolo, R., Lohmeyer, F.M., Cavaliere, C., and Ria, F. (2023). strategies to prevent the recurrence of nasal polys after surgical treatment: An update and in vitro study on growth inhibition of fibroblasts. J. Clin. Med., 12.","DOI":"10.3390\/jcm12082841"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"573","DOI":"10.2165\/00003495-200161050-00003","article-title":"Topical corticosteroids in nasal polyposis","volume":"61","author":"Badia","year":"2001","journal-title":"Drugs"},{"key":"ref_7","first-page":"345","article-title":"Complementary and integrative treatments. Otolaryngol","volume":"46","author":"Taw","year":"2013","journal-title":"Clin. N. Am."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.bbamcr.2004.05.005","article-title":"Transforming growth factor-beta1 stimulates collagen matrix remodeling through increased adhesive and contractive potential by human renal fibroblasts","volume":"1693","author":"Kondo","year":"2004","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"449","DOI":"10.4168\/aair.2014.6.5.449","article-title":"Prostaglandin E2 Induces IL-6 and IL-8 Production by the EP Receptors\/Akt\/NF-\u03baB Pathways in Nasal Polyp-Derived Fibroblasts","volume":"6","author":"Cho","year":"2014","journal-title":"Allergy Asthma Immunol. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1080\/00016489850182945","article-title":"Comparative assessment of cell proliferation and accumulation of extracellular matrix in nasal polyps","volume":"538","author":"Nakagawa","year":"1998","journal-title":"Acta Otolaryngol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"247","DOI":"10.4103\/0973-029X.84516","article-title":"Heterogenecity of fibroblasts","volume":"15","author":"Ravikanth","year":"2011","journal-title":"J. Oral Maxillofac. Pathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S1471-4906(01)01863-4","article-title":"Fibroblasts regulate the switch from acute resolving to chronic persistent inflammation","volume":"22","author":"Buckley","year":"2001","journal-title":"Trends Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Francesca Cialdai, F., Chiara Risaliti, C., and Monici, M. (2022). Role of fibroblasts in wound healing and tissue remodeling on Earth and in space. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.958381"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1186\/s13075-019-2088-3","article-title":"Enhanced angiogenic function in response to fibroblasts from psoriatic arthritis synovium compared to rheumatoid arthritis","volume":"21","author":"Fromm","year":"2019","journal-title":"Arthritis Res. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"123","DOI":"10.3389\/fphar.2014.00123","article-title":"Fibroblasts in fibrosis: Novel roles and mediators","volume":"5","author":"Kendall","year":"2014","journal-title":"Front. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1097\/FJC.0b013e3182116e39","article-title":"Fibroblasts and myofibroblasts: What are we talking about?","volume":"57","author":"Baum","year":"2011","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_17","first-page":"301","article-title":"Fibroblasts and myofibroblasts in wound healing","volume":"7","author":"Darby","year":"2014","journal-title":"Clin. Cosmet. Investig. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"348","DOI":"10.2500\/ajra.2010.24.3520","article-title":"The effect of macrolides on myofibroblast differentiation and collagen production in nasal polyp-derived fibroblasts","volume":"24","author":"Park","year":"2010","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/j.immuni.2015.10.012","article-title":"Pulmonary Epithelial Cell-Derived Cytokine TGF-beta1 Is a Critical Cofactor for Enhanced Innate Lymphoid Cell Function","volume":"43","author":"Denney","year":"2015","journal-title":"Immunity"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1016\/j.bbadis.2009.06.004","article-title":"TGF- and fibrosis in different organs\u2014Molecular pathway imprints","volume":"1792","author":"Pohlers","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.pharmthera.2014.11.001","article-title":"Targeting the TGFbeta pathway for cancer therapy","volume":"147","author":"Neuzillet","year":"2015","journal-title":"Pharmacol. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1096\/fj.201902354R","article-title":"Transforming growth factor beta induces fibroblasts to express and release the immunomodulatory protein PD-L1 into extracellular vesicles","volume":"34","author":"Kang","year":"2020","journal-title":"FASEB J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1001\/archotol.124.12.1361","article-title":"Expression of the transforming growth factor beta isoforms in inflammatory cells of nasal polyps","volume":"124","author":"Coste","year":"1998","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Omura, S., Iwai, Y., Hirano, A., Nakagawa, A., Awaya, J., Tsuchya, H., Takahashi, Y., and Masuma, R. A new alkaloid AM-2282 of Streptomyces origin. Taxonomy, fermentation, isolation and preliminary characterization. J. Antibiot. 1977, 30, 275\u2013282.","DOI":"10.7164\/antibiotics.30.275"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/0165-6147(89)90263-0","article-title":"Staurosporine, K-252 and UCN-01: Potent but nonspecific inhibitors of protein kinase","volume":"10","author":"Burgess","year":"1989","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_26","first-page":"2893","article-title":"Induction of apoptosis by staurpsorine involves the inhibition of expression of the major cell cycle proteins at the G2\/M checkpoint accompanied by alterations in Erk and Akt kinase activities","volume":"29","author":"Antonsson","year":"2009","journal-title":"Anticancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1006\/phrs.2000.0700","article-title":"Molecular mechanism of staurosporine-induced apoptosis in osteoblasts","volume":"42","author":"Chae","year":"2000","journal-title":"Pharmacol. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1111\/j.1745-7254.2005.00205.x","article-title":"Effect of protein kinase C alpha, caspase-3, and survivin on apoptosis of oral cancer cells induced by staurosporine","volume":"26","author":"Zhang","year":"2005","journal-title":"Acta Pharmacologica. Sinica."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1016\/j.chembiol.2015.11.004","article-title":"Differential Regulation of Specific Sphingolipids in Colon Cancer Cells during Staurosporine-Induced Apoptosis","volume":"22","author":"Lizardo","year":"2015","journal-title":"Chem. Biol."},{"key":"ref_30","first-page":"745","article-title":"Role of extracellular matrix in regulation of staurosporine-induced apoptosis in breast cancer cells","volume":"13","author":"Vasaturo","year":"2005","journal-title":"Oncol. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.lfs.2015.04.019","article-title":"Anti-tumor activity of staurosporine in the tumor microenvironment of cervical cancer: An in vitro study","volume":"133","author":"Yadav","year":"2015","journal-title":"Life Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"35962","DOI":"10.18632\/oncotarget.26311","article-title":"Staurosporine, an inhibitor of hormonally up-regulated neu-associated kinase","volume":"9","author":"Zambrano","year":"2018","journal-title":"Oncotarget"},{"key":"ref_33","first-page":"3991","article-title":"High-efficiency liposomal encapsulation of a tyrosine kinase inhibitor leads to improved in vivo toxicity and tumor response profile","volume":"8","author":"Mukthavaram","year":"2013","journal-title":"Int. J. Nanomed."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Cui, T., Lin, S., Wang, Z., Fu, P., Wang, C., and Zhu, W. (2022). Cytotoxic indolocarbazoles from a marine-derived Streptomyces sp. OUCMDZ-5380. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.957473"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Meng, J., Zhou, P., Liu, Y., Liu, F., Yi, X., Liu, S., Holtappels, G., Bachert, C., and Zhang, N. (2013). The development of nasal polyp disease involves early nasal mucosal inflammation and remodelling. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0082373"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Park, S.K., Jin, Y.D., Park, Y.K., Yeon, S.H., Xu, J., Han, R.N., Rha, K.S., and Kim, Y.M. (2017). IL-25-induced activation of nasal fibroblast and its association with the remodeling of chronic rhinosinusitis with nasal polyposis. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0181806"},{"key":"ref_37","first-page":"2213","article-title":"Effect of phlorotannins on myofibroblast differentiation and ECM protein expression in transforming growth factor \u03b21-induced nasal polyp-derived fibroblasts","volume":"42","author":"Park","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Jung, H., Lee, D.-S., Park, S.K., Choi, J.S., Jung, W.-K., Park, W.S., and Choi, I.-W. (2018). Fucoxanthin Inhibits Myofibroblast Differentiation and Extracellular Matrix Production in Nasal Polyp-Derived Fibroblasts via Modulation of Smad-Dependent and Smad-Independent Signaling Pathways. Mar. Drugs, 16.","DOI":"10.3390\/md16090323"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.pupt.2009.04.002","article-title":"N-acetyl-L-cysteine inhibits TGF-\u03b21-induced profibrotic responses in fibroblasts","volume":"22","author":"Sugiura","year":"2009","journal-title":"Pulm. Pharmacol. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1097\/00005537-200310000-00027","article-title":"IL-11 and IL-17 expression in nasal polyps: Relationship to collagen deposition and suppression by intranasal fluticasone propionate","volume":"113","author":"Molet","year":"2003","journal-title":"Laryngoscope"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1001\/archotol.124.5.513","article-title":"Effect of fluticasone in severe polyposis","volume":"124","author":"Lund","year":"1998","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4007","DOI":"10.1016\/j.cell.2023.07.036","article-title":"TGF-\u00df signaling in health and disease","volume":"186","author":"Sheppard","year":"2023","journal-title":"Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.ijporl.2006.08.018","article-title":"Vascular endothelial growth factor and children featuring nasal polyps","volume":"71","author":"Hu","year":"2007","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"82","DOI":"10.18787\/jr.2021.00400","article-title":"The Roles of Vascular Endothelial Growth Factor, Angiostatin, and Endostatin in Nasal Polyp Development","volume":"29","author":"Hong","year":"2022","journal-title":"J. Rhinol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.jss.2008.04.023","article-title":"The Role of Vascular Endothelial Growth Factor in Wound Healing","volume":"153","author":"Bao","year":"2009","journal-title":"J. Surg. Res."},{"key":"ref_46","first-page":"1","article-title":"Tissue remodelling in chronic rhinosinusitis\u2014Review of literature","volume":"73","author":"Radajewski","year":"2019","journal-title":"Otolaryngol. Pol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1007\/s00011-010-0271-8","article-title":"Angiogenesis in chronic rhinosinusitis with nasal polyps and in antrochoanal polyps","volume":"60","author":"Hirshoren","year":"2011","journal-title":"Inflamm. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5815","DOI":"10.3390\/cimb44110395","article-title":"Antifibrosis Efficacy of Apo-9-Fucoxanthinone-Contained Sargassum horneri Ethanol Extract on Nasal Polyp: An In Vitro and Ex Vivo Organ Culture Assay","volume":"44","author":"Yim","year":"2022","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_49","first-page":"1950","article-title":"Anti-inhibitory potential of an ethanolic extract of Distromium decumbens on pro-inflammatory cytokine production in Pseudomonas aeruginosa lipopolysaccharide-stimulated nasal polyp-derived fibroblasts","volume":"40","author":"Lee","year":"2017","journal-title":"Int. J. Mol. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"402","DOI":"10.2500\/ajr.2007.21.3050","article-title":"Organ culture at the air-liquid interface maintains structural and functional integrities of inflammatory and fibrovascular cells of nasal polyps","volume":"21","author":"Park","year":"2007","journal-title":"Am. J. Rhinol."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/22\/1\/39\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:44:37Z","timestamp":1760103877000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/22\/1\/39"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,11]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["md22010039"],"URL":"https:\/\/doi.org\/10.3390\/md22010039","relation":{},"ISSN":["1660-3397"],"issn-type":[{"type":"electronic","value":"1660-3397"}],"subject":[],"published":{"date-parts":[[2024,1,11]]}}}