In:
ChemBioChem, Wiley, Vol. 19, No. 8 ( 2018-04-16), p. 851-864
Abstract:
Pentachloropseudilin (PClP) is a chlorinated phenylpyrrole compound that was first isolated from Actinoplanes (ATCC33002), and its structure has been confirmed by chemical synthesis. PClP shows broad antimicrobial activity against Gram‐negative and Gram‐positive bacteria, protozoa, fungi, and yeast. In mammalian cells, PClP is known to act as a reversible and allosteric inhibitor of myosin 1c (Myo1c). Herein, we report that PCIP is a potent inhibitor of transforming growth factor‐β (TGF‐β)‐stimulated signaling. PCIP inhibits TGF‐β‐stimulated Smad2/3 phosphorylation and plasminogen activator inhibitor‐1 (PAI‐1) promoter activation with an IC 50 of 0.1 μ m in target cells (A549, HepG2, and Mv1Lu cells). In addition, PCIP attenuates TGF‐β‐stimulated expression of vimentin, N ‐cadherin, and fibronectin and, thus, blocks TGF‐β‐induced epithelial to mesenchymal transition (EMT) in these cells. Furthermore, cell‐surface labeling and immunoblot analysis indicates that PCIP suppresses TGF‐β‐stimulated cellular responses by attenuating cell‐surface expression of the type II TGF‐β receptor through accelerating caveolae‐mediated internalization followed by primarily lysosome‐dependent degradation of the receptor, as demonstrated by sucrose density gradient analysis and immune fluorescence staining.
Type of Medium:
Online Resource
ISSN:
1439-4227
,
1439-7633
DOI:
10.1002/cbic.201700693
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2020469-3
SSG:
12
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