AI Article Synopsis
- Alantolactone, a type of sesquiterpene lactone, inhibits TNF receptor 1 (TNF-R1) expression in human lung adenocarcinoma A549 cells, independent of three adaptor proteins.
- The down-regulation of TNF-R1 by alantolactone is influenced by its ability to promote the shedding of the receptor's ectodomain and is blocked by a TNF-α-converting enzyme inhibitor.
- Additionally, the study highlights that the α-methylene-γ-lactone moiety is essential for the ectodomain shedding of TNF-R1 and is also observed in other similar compounds like parthenolide and costunolide.
Article Abstract
Alantolactone is a eudesmane-type sesquiterpene lactone containing an α-methylene-γ-lactone moiety. Previous studies showed that alantolactone inhibits the nuclear factor κB (NF-κB) signaling pathway by targeting the inhibitor of NF-κB (IκB) kinase. However, in the present study, we demonstrated that alantolactone selectively down-regulated the expression of tumor necrosis factor (TNF) receptor 1 (TNF-R1) in human lung adenocarcinoma A549 cells. Alantolactone did not affect the expression of three adaptor proteins recruited to TNF-R1. The down-regulation of TNF-R1 expression by alantolactone was suppressed by an inhibitor of TNF-α-converting enzyme. Alantolactone increased the soluble forms of TNF-R1 that were released into the culture medium as an ectodomain. The structure-activity relationship of eight eudesmane derivatives revealed that an α-methylene-γ-lactone moiety was needed to promote TNF-R1 ectodomain shedding. In addition, parthenolide and costunolide, two sesquiterpene lactones with an α-methylene-γ-lactone moiety, increased the amount of soluble TNF-R1. Therefore, the present results demonstrate that sesquiterpene lactones with an α-methylene-γ-lactone moiety can down-regulate the expression of TNF-R1 by promoting its ectodomain shedding in A549 cells.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11053566 | PMC |
| http://dx.doi.org/10.3390/molecules29081866 | DOI Listing |
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