The Inhibition Effect and Mechanism of Staurosporine Isolated from Sp. SNC087 Strain on Nasal Polyp

Overview

Journal Mar Drugs

Publisher MDPI

Specialties Biology
Pharmacology

Date 2024 Jan 22

PMID 38248664

Authors

Grace Choi

Eun-Young Lee

Dawoon Chung

Kichul Cho

Woon-Jong Yu

Sang-Jip Nam

Seong-Kook Park

Il-Whan Choi

Affiliations

Soon will be listed here.

Abstract

This study aims to explore the potential inhibition effects of staurosporine isolated from a 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-β1 in the presence of staurosporine. The levels of α-smooth muscle actin (α-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-β1 stimulated the production of Col-1, fibronectin, and α-SMA and was attenuated by staurosporine pretreatment. Furthermore, these inhibitory effects were mediated by modulation of the signaling pathway of Smad 2 in TGF-β1-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's role in nasal polyp management and provide insights into its mechanisms of action.

References

Lund V, Flood J, Sykes A, Richards D . Effect of fluticasone in severe polyposis. Arch Otolaryngol Head Neck Surg. 1998; 124(5):513-8. DOI: 10.1001/archotol.124.5.513. View

Mukthavaram R, Jiang P, Saklecha R, Simberg D, Bharati I, Nomura N . High-efficiency liposomal encapsulation of a tyrosine kinase inhibitor leads to improved in vivo toxicity and tumor response profile. Int J Nanomedicine. 2013; 8:3991-4006. PMC: 3808212. DOI: 10.2147/IJN.S51949. View

Park S, Lee W, Yang Y . Organ culture at the air-liquid interface maintains structural and functional integrities of inflammatory and fibrovascular cells of nasal polyps. Am J Rhinol. 2007; 21(4):402-7. DOI: 10.2500/ajr.2007.21.3050. View

Hwang C, Park S, Cho H, Park D, Yoon J, Kim C . Eosinophil extracellular trap formation is closely associated with disease severity in chronic rhinosinusitis regardless of nasal polyp status. Sci Rep. 2019; 9(1):8061. PMC: 6542829. DOI: 10.1038/s41598-019-44627-z. View

Badia L, Lund V . Topical corticosteroids in nasal polyposis. Drugs. 2001; 61(5):573-8. DOI: 10.2165/00003495-200161050-00003. View

Goulioumis A, Kourelis K, Gkorpa M, Danielides V . Pathogenesis of Nasal Polyposis: Current Trends. Indian J Otolaryngol Head Neck Surg. 2023; 75(Suppl 1):733-741. PMC: 10188681. DOI: 10.1007/s12070-022-03247-2. View

Zhang Y, Yu S, Ou-Yang J, Xia D, Wang M, Li J . Effect of protein kinase C alpha, caspase-3, and survivin on apoptosis of oral cancer cells induced by staurosporine. Acta Pharmacol Sin. 2005; 26(11):1365-72. DOI: 10.1111/j.1745-7254.2005.00205.x. View

Park J, Choi G, Yim M, Lee J, Yoo J, Park W . Effect of phlorotannins on myofibroblast differentiation and ECM protein expression in transforming growth factor β1‑induced nasal polyp‑derived fibroblasts. Int J Mol Med. 2018; 42(4):2213-2220. DOI: 10.3892/ijmm.2018.3770. View

Darby I, Laverdet B, Bonte F, Desmouliere A . Fibroblasts and myofibroblasts in wound healing. Clin Cosmet Investig Dermatol. 2014; 7:301-11. PMC: 4226391. DOI: 10.2147/CCID.S50046. View

10.

Stevens W, Schleimer R, Chandra R, Peters A . Biology of nasal polyposis. J Allergy Clin Immunol. 2014; 133(5):1503, 1503.e1-4. PMC: 4422376. DOI: 10.1016/j.jaci.2014.03.022. View

11.

Chae H, Kang J, Byun J, Han K, Kim D, Oh S . Molecular mechanism of staurosporine-induced apoptosis in osteoblasts. Pharmacol Res. 2000; 42(4):373-81. DOI: 10.1006/phrs.2000.0700. View

12.

Del Solar V, Lizardo D, Li N, Hurst J, Brais C, Atilla-Gokcumen G . Differential Regulation of Specific Sphingolipids in Colon Cancer Cells during Staurosporine-Induced Apoptosis. Chem Biol. 2015; 22(12):1662-70. DOI: 10.1016/j.chembiol.2015.11.004. View

13.

Pohlers D, Brenmoehl J, Loffler I, Muller C, Leipner C, Schultze-Mosgau S . TGF-beta and fibrosis in different organs - molecular pathway imprints. Biochim Biophys Acta. 2009; 1792(8):746-56. DOI: 10.1016/j.bbadis.2009.06.004. View

14.

Molet S, Hamid Q, Hamilos D . IL-11 and IL-17 expression in nasal polyps: relationship to collagen deposition and suppression by intranasal fluticasone propionate. Laryngoscope. 2003; 113(10):1803-12. DOI: 10.1097/00005537-200310000-00027. View

15.

Vasaturo F, Malacrino C, Sallusti E, Coppotelli G, Birarelli P, Giuffrida A . Role of extracellular matrix in regulation of staurosporine-induced apoptosis in breast cancer cells. Oncol Rep. 2005; 13(4):745-50. DOI: 10.3892/or.13.4.745. View

16.

Yim M, Lee J, Ko S, Kim H, Kim J, Park S . Antifibrosis Efficacy of Apo-9-Fucoxanthinone-Contained Ethanol Extract on Nasal Polyp: An In Vitro and Ex Vivo Organ Culture Assay. Curr Issues Mol Biol. 2022; 44(11):5815-5826. PMC: 9689088. DOI: 10.3390/cimb44110395. View

17.

Bao P, Kodra A, Tomic-Canic M, Golinko M, Ehrlich H, Brem H . The role of vascular endothelial growth factor in wound healing. J Surg Res. 2008; 153(2):347-58. PMC: 2728016. DOI: 10.1016/j.jss.2008.04.023. View

18.

Rizzi A, Gammeri L, Cordiano R, Valentini M, Centrone M, Marrone S . Therapeutic Strategies to Prevent the Recurrence of Nasal Polyps after Surgical Treatment: An Update and In Vitro Study on Growth Inhibition of Fibroblasts. J Clin Med. 2023; 12(8). PMC: 10142691. DOI: 10.3390/jcm12082841. View

19.

Kondo S, Kagami S, Urushihara M, Kitamura A, Shimizu M, Strutz F . Transforming growth factor-beta1 stimulates collagen matrix remodeling through increased adhesive and contractive potential by human renal fibroblasts. Biochim Biophys Acta. 2004; 1693(2):91-100. DOI: 10.1016/j.bbamcr.2004.05.005. View

20.

Baum J, Duffy H . Fibroblasts and myofibroblasts: what are we talking about?. J Cardiovasc Pharmacol. 2011; 57(4):376-9. PMC: 3077448. DOI: 10.1097/FJC.0b013e3182116e39. View