Suppression of TGFβ-Induced Interleukin-6 Secretion by Sinulariolide from Soft Corals through Attenuation of the p38–NF-kB Pathway in Carcinoma Cells
Sinulariolide (SC-1) is a natural product extracted from the cultured-type soft coral <i>Sinularia flexibilis</i> and possesses anti-inflammation, anti-proliferative, and anti-migratory in several types of cancer cells. However, the molecular pathway behind its effects on inflammation re...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/14/11656 |
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| author | Jenq-Lin Yang Weng-Ling Lin Shun-Ban Tai Yi-Siang Ciou Chih-Ling Chung Jih-Jung Chen Pei-Feng Liu Ming-Wei Lin Chun-Lin Chen |
| author_facet | Jenq-Lin Yang Weng-Ling Lin Shun-Ban Tai Yi-Siang Ciou Chih-Ling Chung Jih-Jung Chen Pei-Feng Liu Ming-Wei Lin Chun-Lin Chen |
| author_sort | Jenq-Lin Yang |
| collection | DOAJ |
| description | Sinulariolide (SC-1) is a natural product extracted from the cultured-type soft coral <i>Sinularia flexibilis</i> and possesses anti-inflammation, anti-proliferative, and anti-migratory in several types of cancer cells. However, the molecular pathway behind its effects on inflammation remains poorly understood. Since inflammatory cytokines such as TGFβ, TNFα, IL-1, IL-6, and IL-8 activate transcription factors such as Smads, NF-κB, STAT3, Snail, Twist, and Zeb that drive the epithelial-to-mesenchymal transition (EMT), in this study, we focus on the investigation in effects of SC-1 on TGFβ-induced interleukin-6 (IL-6) releases in an in vitro cell culture model. We showed that both intracellular IL-6 expression and secretion were stimulated by TGFβ and associated with strong upregulation of IL-6 mRNA and increased transcription in A549 cells. SC-1 blocked TGFβ-induced secretion of IL-6 while showing no effect on the induction of fibronectin and plasminogen activator inhibitor-1 genes, indicating that SC-1 interferes with only a subset of TGFβ activities. In addition, SC-1 inhibits TGFβ-induced IL-6 by suppressing p38 MAPK signaling and subsequently inhibits NF-κB and its nuclear translocation without affecting the canonical Smad pathway and receptor turnover. Overall, these data suggest that p38 may involve in the inhibition of SC-1 in IL-6 release, thus illustrating an inhibitory effect for SC-1 in the suppression of inflammation, EMT phenotype, and tumorigenesis. |
| first_indexed | 2024-03-11T00:59:44Z |
| format | Article |
| id | doaj.art-781a540578fc402a9c2ee773aaad0f13 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T00:59:44Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-781a540578fc402a9c2ee773aaad0f132023-11-18T19:42:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-07-0124141165610.3390/ijms241411656Suppression of TGFβ-Induced Interleukin-6 Secretion by Sinulariolide from Soft Corals through Attenuation of the p38–NF-kB Pathway in Carcinoma CellsJenq-Lin Yang0Weng-Ling Lin1Shun-Ban Tai2Yi-Siang Ciou3Chih-Ling Chung4Jih-Jung Chen5Pei-Feng Liu6Ming-Wei Lin7Chun-Lin Chen8Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, TaiwanDepartment of Pathology, Kaohsiung Armed Forces General Hospital, Kaohsiung 80284, TaiwanDepartment of Biological Sciences, National Sun Yat-Sen University, Kaohsiung 80424, TaiwanDepartment of Biological Sciences, National Sun Yat-Sen University, Kaohsiung 80424, TaiwanDepartment of Biological Sciences, National Sun Yat-Sen University, Kaohsiung 80424, TaiwanDepartment of Pharmacy, School of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei 112304, TaiwanDepartment of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 80756, TaiwanDepartment of Medical Research, E-Da Hospital/E-Da Cancer Hospital, Kaohsiung 82445, TaiwanDepartment of Biological Sciences, National Sun Yat-Sen University, Kaohsiung 80424, TaiwanSinulariolide (SC-1) is a natural product extracted from the cultured-type soft coral <i>Sinularia flexibilis</i> and possesses anti-inflammation, anti-proliferative, and anti-migratory in several types of cancer cells. However, the molecular pathway behind its effects on inflammation remains poorly understood. Since inflammatory cytokines such as TGFβ, TNFα, IL-1, IL-6, and IL-8 activate transcription factors such as Smads, NF-κB, STAT3, Snail, Twist, and Zeb that drive the epithelial-to-mesenchymal transition (EMT), in this study, we focus on the investigation in effects of SC-1 on TGFβ-induced interleukin-6 (IL-6) releases in an in vitro cell culture model. We showed that both intracellular IL-6 expression and secretion were stimulated by TGFβ and associated with strong upregulation of IL-6 mRNA and increased transcription in A549 cells. SC-1 blocked TGFβ-induced secretion of IL-6 while showing no effect on the induction of fibronectin and plasminogen activator inhibitor-1 genes, indicating that SC-1 interferes with only a subset of TGFβ activities. In addition, SC-1 inhibits TGFβ-induced IL-6 by suppressing p38 MAPK signaling and subsequently inhibits NF-κB and its nuclear translocation without affecting the canonical Smad pathway and receptor turnover. Overall, these data suggest that p38 may involve in the inhibition of SC-1 in IL-6 release, thus illustrating an inhibitory effect for SC-1 in the suppression of inflammation, EMT phenotype, and tumorigenesis.https://www.mdpi.com/1422-0067/24/14/11656sinulariolideTGF-βinterleukin-6 |
| spellingShingle | Jenq-Lin Yang Weng-Ling Lin Shun-Ban Tai Yi-Siang Ciou Chih-Ling Chung Jih-Jung Chen Pei-Feng Liu Ming-Wei Lin Chun-Lin Chen Suppression of TGFβ-Induced Interleukin-6 Secretion by Sinulariolide from Soft Corals through Attenuation of the p38–NF-kB Pathway in Carcinoma Cells International Journal of Molecular Sciences sinulariolide TGF-β interleukin-6 |
| title | Suppression of TGFβ-Induced Interleukin-6 Secretion by Sinulariolide from Soft Corals through Attenuation of the p38–NF-kB Pathway in Carcinoma Cells |
| title_full | Suppression of TGFβ-Induced Interleukin-6 Secretion by Sinulariolide from Soft Corals through Attenuation of the p38–NF-kB Pathway in Carcinoma Cells |
| title_fullStr | Suppression of TGFβ-Induced Interleukin-6 Secretion by Sinulariolide from Soft Corals through Attenuation of the p38–NF-kB Pathway in Carcinoma Cells |
| title_full_unstemmed | Suppression of TGFβ-Induced Interleukin-6 Secretion by Sinulariolide from Soft Corals through Attenuation of the p38–NF-kB Pathway in Carcinoma Cells |
| title_short | Suppression of TGFβ-Induced Interleukin-6 Secretion by Sinulariolide from Soft Corals through Attenuation of the p38–NF-kB Pathway in Carcinoma Cells |
| title_sort | suppression of tgfβ induced interleukin 6 secretion by sinulariolide from soft corals through attenuation of the p38 nf kb pathway in carcinoma cells |
| topic | sinulariolide TGF-β interleukin-6 |
| url | https://www.mdpi.com/1422-0067/24/14/11656 |
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