Sinulariolide, a Compound from Soft Corals, Suppresses TGFβ-Induced Interleukin-6 Secretion in Carcinoma Cells

Sinulariolide is a natural product extracted from the soft coral Sinularia flexibilis and has anti-inflammatory, anti-proliferative and anti-migratory effects on several types of cancer cells. However, the underlying mechanism of its anti-inflammatory effects is not well understood. In this study, we focus on investigating the effects of sinulariolide on TGFβ-induced release of interleukin 6 (IL-6) in an in vitro cell culture model. We found that TGFβ stimulated the expression and secretion of IL-6 and was associated with increased transcription of IL-6 mRNA in A549 cells. Sinulariolide blocked TGFβ-induced IL-6 secretion without affecting the induction of fibronectin and plasminogen activator inhibitor-1 genes, indicating that it only interferes with a subset of TGFβ activities. Moreover, sinulariolide inhibits TGFβ-induced IL-6 by suppressing p38 MAPK signaling and subsequent NF-κB and its nuclear translocation, while having no effect on the canonical Smad pathway or receptor turnover. Our data suggests that p38 is involved in the inhibition of sinulariolide- mediated IL-6 release, highlighting its potential in suppressing inflammation, EMT phenotype, and tumorigenesis.

 

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Conflict of Interest

The author declares no conflict of interest.

Publikationsverlauf

Artikel online veröffentlicht:
16. November 2023