Suppression of TGFβ-Induced Interleukin-6 Secretion by Sinulariolide from Soft Corals through Attenuation of the p38–NF-kB Pathway in Carcinoma Cells

Author:

Yang Jenq-Lin1ORCID,Lin Weng-Ling2,Tai Shun-Ban34,Ciou Yi-Siang3,Chung Chih-Ling3ORCID,Chen Jih-Jung56ORCID,Liu Pei-Feng7,Lin Ming-Wei8,Chen Chun-Lin3910ORCID

Affiliation:

1. Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan

2. Department of Pathology, Kaohsiung Armed Forces General Hospital, Kaohsiung 80284, Taiwan

3. Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan

4. Division of Rheumatology, Immunology and Allergy, Department of Internal Medicine, Zuoying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung 81342, Taiwan

5. Department of Pharmacy, School of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan

6. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404332, Taiwan

7. Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 80756, Taiwan

8. Department of Medical Research, E-Da Hospital/E-Da Cancer Hospital, Kaohsiung 82445, Taiwan

9. Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan

10. Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80756, Taiwan

Abstract

Sinulariolide (SC-1) is a natural product extracted from the cultured-type soft coral Sinularia flexibilis 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.

Funder

Kaohsiung Chang Gung Memorial Hospital Research Project

Ministry of Science and Technology of Taiwan

The Zuoying Branch of Kaohsiung Armed Forces General Hospital Research Project

The NSYSU–KMU Joint Research Project

The Kaohsiung Armed Forces General Hospital Research Project

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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1. Androgen Signaling in Prostate Cancer: When a Friend Turns Foe;Endocrine, Metabolic & Immune Disorders - Drug Targets;2024-05-31

2. NF-κB in the Radiation Response of A549 Non-Small Cell Lung Cancer Cells to X-rays and Carbon Ions under Hypoxia;International Journal of Molecular Sciences;2024-04-19

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