Biomolecules & Therapeutics

  • 제32권5호
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  • Pages.540-545
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  • 2024
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  • 1976-9148(pISSN)
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  • 2005-4483(eISSN)
한국응용약물학회 (The Korean Society of Applied Pharmacology)
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Pyronaridine Inhibited MUC5AC Mucin Gene Expression by Regulation of Nuclear Factor Kappa B Signaling Pathway in Human Pulmonary Mucoepidermoid Cells

  • Rajib Hossain (Department of Pharmacology, School of Medicine, Chungnam National University) ;
  • Hyun Jae Lee (Smith Liberal Arts College and Department of Addiction Science Graduate School, Sahmyook University) ;
  • Choong Jae Lee (Department of Pharmacology, School of Medicine, Chungnam National University)
  • 투고 : 2024.05.04
  • 심사 : 2024.06.19
  • 발행 : 2024.09.01
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초록

In this study, the potential effects of pyronaridine, an antimalarial agent, on airway MUC5AC mucin gene expression were investigated. The human pulmonary epithelial NCI-H292 cells were pretreated with pyronaridine for 30 min and then stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 h. The effect of pyronaridine on the PMA-induced nuclear factor kappa B (NF-κB) signaling pathway was also examined. Pyronaridine inhibited glycoprotein production and mRNA expression of MUC5AC mucins induced by PMA through the inhibition of degradation of inhibitory kappa Bα and NF-κB p65 nuclear translocation. These results suggest that pyronaridine suppresses gene expression of mucin through regulation of the NF-κB signaling pathway in human pulmonary epithelial cells.

키워드

과제정보

This research was supported by the NRF-2014R1A6A1029617 Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education.

참고문헌

  1. Ardanuy, J., Johnson, R., Dillen, C., Taylor, L., Hammond, H., Weston, S. and Frieman, M. (2023) Pyronaridine tetraphosphate is an efficacious antiviral and anti-inflammatory active against multiple highly pathogenic coronaviruses. mBio 14, e0158723.
  2. Fujisawa, T., Velichko, S., Thai, P., Hung, L. Y., Huang, F. and Wu, R. (2009) Regulation of airway MUC5AC expression by IL-1beta and IL-17A; the NF-kappa B paradigm. J. Immunol. 183, 6236-6243.
  3. Garvin, L. M., Chen, Y., Damsker, J. M. and Rose, M. C. (2016) A novel dissociative steroid VBP15 reduces MUC5AC gene expression in airway epithelial cells but lacks the GRE mediated transcriptional properties of dexamethasone. Pulm. Pharmacol. Ther. 38, 17-26.
  4. Ghosalkar, J., Sonawane, V., Pisal, T., Achrekar, S., Pujari, R., Chugh, A., Shastry, P. and Joshi, K. (2022) Prostate apoptosis response-4 (Par-4): a novel target in pyronaridine-induced apoptosis in glioblastoma (GBM) cells. Cancers (Basel) 14, 3198.
  5. Hossain, R., Kim, K. I., Li, X., Lee, H. J. and Lee, C. J. (2022a) Involvement of IKK/IkBα/NF-kB p65 signaling into the regulative effect of engeletin on MUC5AC mucin gene expression in human airway epithelial cells. Biomol. Ther. (Seoul) 30, 473-478.
  6. Hossain, R., Kim, K. I., Jin, F., Lee, H. J. and Lee, C. J. (2022b) Betulin, an anti-inflammatory triterpenoid compound, regulates MUC5AC mucin gene expression through NF-kB signaling in human airway epithelial cells. Biomol. Ther. (Seoul) 30, 540-545.
  7. Ishinaga, H., Takeuchi, K., Kishioka, C., Suzuki, S., Basbaum, C. and Majima, Y. (2005) Pranlukast inhibits NF-kappaB activation and MUC2 gene expression in cultured human epithelial cells. Pharmacology 73, 89-96.
  8. Kim, K. I., Hossain, R., Ryu, J., Lee, H. J. and Lee, C. J. (2023) Regulation of the gene expression of airway MUC5AC mucin through NF-κB signaling pathway by artesunate, an antimalarial agent. Biomol. Ther. (Seoul) 31, 544-549.
  9. Kim, E. J., Yoon, Y. P., Woo, K. W., Kim, J. H., Min, S. Y., Lee, H. J., Lee, S. K., Hong, J. H., Lee, K. R. and Lee, C. J. (2016) Verticine, ebeiedine and suchengbeisine isolated from the bulbs of Fritillaria thunbergii Miq. inhibited the gene expression and production of MUC5AC mucin from human airway epithelial cells. Phytomedicine 23, 95-104.
  10. Kim, J. O., Sikder, M. A., Lee, H. J., Rahman, M., Kim, J. H., Chang, G. T. and Lee, C. J. (2012) Phorbol ester or epidermal growth factor-induced MUC5AC mucin gene expression and production from airway epithelial cells are inhibited by pyronaridine and wogonin. Phytother. Res. 26, 1784-1788.
  11. Kingsmore, K. M., Grammer, A. C. and Lipsky, P. E. (2020) Drug repurposing to improve treatment of rheumatic autoimmune inflammatory diseases. Nat. Rev. Rheumatol. 16, 32-52.
  12. Krishna, S., Augustin, Y., Wang, J., Xu, C., Staines, H. M., Platteeuw, H., Kamarulzaman, A., Sall, A. and Kremsner, P. (2021) Repurposing antimalarials to tackle the COVID-19 pandemic. Trends Parasitol. 37, 8-11.
  13. Kurakula, K., Hamers, A. A., van Loenen, P. and de Vries, C. J. (2015) 6-Mercaptopurine reduces cytokine and Muc5ac expression involving inhibition of NF-kB activation in airway epithelial cells. Respir. Res. 16, 73.
  14. Laos, S., Baeckstrom, D. and Hansson, G. C. (2006) Inhibition of NFkappaB activation and chemokine expression by the leukocyte glycoprotein, CD43, in colon cancer cells. Int. J. Oncol. 28, 695-704.
  15. Lee, H. J., Park, J. S., Yoon, Y. P., Shin, Y. J., Lee, S. K., Kim, Y. S., Hong, J. H., Son, K. H. and Lee, C. J. (2015) Dioscin and methyl-protodioscin isolated from the root of Asparagus cochinchinensis suppressed the gene expression and production of airway MUC5AC mucin induced by phorbol ester and growth factor. Phytomedicine 22, 568-572.
  16. Li, J. D., Dohrman, A. F., Gallup, M., Miyata, S., Gum, J. R., Kim, Y. S., Nadel, J. A., Prince, A. and Basbaum, C. B. (1997) Transcriptional activation of mucin by Pseudomonas aeruginosa lipopolysaccharide in the pathogenesis of cystic fibrosis lung disease. Proc. Natl. Acad. Sci. U. S. A. 94, 967-972.
  17. Li, X., Jin, F., Lee, H. J. and Lee, C. J. (2020) Recent advances in the development of novel drug candidates for regulating the secretion of pulmonary mucus. Biomol. Ther. (Seoul) 28, 293-301.
  18. Mann, T. S., Larcombe, A. N., Wang, K. C., Shamsuddin, D., Landwehr, K. R., Noble, P. B. and Henry, P. J. (2022) Azithromycin inhibits mucin secretion, mucous metaplasia, airway inflammation, and airways hyperresponsiveness in mice exposed to house dust mite extract. Am. J. Physiol. Lung Cell. Mol. Physiol. 322, L683-L698.
  19. Rank, L., Puhl, A. C., Havener, T. M., Anderson, E., Foil, D. H., Zorn, K. M., Monakhova, N., Riabova, O., Hickey, A. J., Makarov, V. and Ekins, S. (2022) Multiple approaches to repurposing drugs for neuroblastoma. Bioorg. Med. Chem. 73, 117043.
  20. Ryu, J., Kim, K. I., Hossain, R., Lee, M., Hong, J. T., Lee, H. J. and Lee, C. J. (2023) Meclofenamate suppresses MUC5AC mucin gene expression by regulating the NF-kB signaling pathway in human pulmonary mucoepidermoid NCI-H292 cells. Biomol. Ther. (Seoul) 31, 306-311.
  21. Ryu, J., Lee, H. J., Park, S. H., Kim, J., Lee, D., Lee, S. K., Kim, Y. S., Hong, J. H., Seok, J. H. and Lee, C. J. (2014) Effects of the root of Platycodon grandiflorum on airway mucin hypersecretion in vivo and platycodin D(3) and deapi-platycodin on production and secretion of airway mucin in vitro. Phytomedicine 21, 529-533.
  22. Ryu, J., Lee, H. J., Park, S. H., Sikder, M. A., Kim, J. O., Hong, J. H., Seok, J. H. and Lee, C. J. (2013) Effect of prunetin on TNF-α-induced MUC5AC mucin gene expression, production, degradation of IκB and translocation of NF-κB p65 in human airway epithelial cells. Tuberc. Respir. Dis. (Seoul) 75, 205-209.
  23. Seo, H. S., Sikder, M. A., Lee, H. J., Ryu, J. and Lee, C. J. (2014) Apigenin inhibits tumor necrosis factor-α-induced production and gene expression of mucin through regulating nuclear factor-kappa b signaling pathway in airway epithelial cells. Biomol. Ther. (Seoul) 22, 525-531.
  24. Shao, M. X., Ueki, I. F. and Nadel, J. A. (2003) TNF-alpha converting enzyme mediated MUC5AC mucin expression in cultured human airway epithelial cells. Proc. Natl. Acad. Sci. U. S. A. 100, 11618-11623.
  25. Sikder, M. A., Lee, H. J., Mia, M. Z., Park, S. H., Ryu, J., Kim, J. H., Min, S. Y., Hong, J. H., Seok, J. H. and Lee, C. J. (2014) Inhibition of TNF-α-induced MUC5AC mucin gene expression and production by wogonin through the inactivation of NF-κB signaling in airway epithelial cells. Phytother. Res. 28, 62-68.
  26. Sprenger, L., Goldmann, T., Vollmer, E., Steffen, A., Wollenberg, B., Zabel, P. and Hauber, H. P. (2011) Dexamethasone and N-acetylcysteine attenuate Pseudomonas aeruginosa-induced mucus expression in human airways. Pulm. Pharmacol. Ther. 24, 232-239.
  27. Takeyama, K., Dabbagh, K., Lee, H., Agusti, C., Lausier, J. A., Ueki, I. F., Grattan, K. M. and Nadel, J. A. (1999) Epidermal growth factor system regulates mucin production in airways. Proc. Natl. Acad. Sci. U. S. A. 96, 3081-3086.
  28. Villanueva, P. J., Gutierrez, D. A., Contreras, L., Parra, K., Segura-Cabrera, A., Varela-Ramirez, A. and Aguilera, R. J. (2021) The antimalarial drug Pyronaridine inhibits topoisomerase II in breast cancer cells and hinders tumor progression in vivo. Clin. Cancer Drugs 8, 50-56.
  29. Wu, D. Y., Wu, R., Reddy, S. P., Lee, Y. C. and Chang, M. M. (2007) Distinctive epidermal growth factor receptor/extracellular regulated kinase-independent and -dependent signaling pathways in the induction of airway mucin 5B and mucin 5AC expression by phorbol 12-myristate 13-Acetate. Am. J. Pathol. 170, 20-32.
  30. Zhong, Z. H., Yi, Z. L., Zhao, Y. D., Wang, J., Jiang, Z. B., Xu, C., Xie, Y. J., He, Q. D., Tong, Z. Y., Yao, X. J., Leung, E. L., Coghi, P. S., Fan, X. X. and Chen, M. (2022) Pyronaridine induces apoptosis in non-small cell lung cancer cells by upregulating death receptor 5 expression and inhibiting epidermal growth factor receptor. Chem. Biol. Drug Des. 99, 83-91.