Galewone, an Anti-Fibrotic Polyketide from Daldinia eschscholzii with an Undescribed Carbon Skeleton

Abstract A novel polyphenolic natural product, galewone, with undescribed carbon skeleton, was isolated as a racemate from the culture of Daldinia eschscholzii IFB-TL01, a fungus obtained from the mantis (Tenodera aridifolia) gut. The galewone structure was elucidated by a combination of MS and NMR spectra, and substantiated by X-ray crystallographic diffraction. The absolute stereochemistry of each galewone enantiomers was determined by the CD spectrum. In compliance of the structural similarities, galewone might be the shunt products of the dalesconol biosynthetic pathway. Both (−)- and ( + )-galewones were evaluated to be anti-fibrotic against activated hepatic stellate cell line, CFSC-8B, with the IC50 values being 3.73 ± 0.21 and 10.10 ± 0.41 μM, respectively. Thus, galewone may serve as a starting molecule for the discovery of new anti-fibrotic drug.

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Glial cell line-derived neurotrophic factor (GDNF) mediates hepatic stellate cell activation via ALK5/Smad signaling

10.1055/s-0039-1695260 ◽

2019 ◽

Author(s):

R Feng ◽

L Tao ◽

W Ma ◽

L Wu ◽

E Seki ◽

...

Keyword(s):

Cell Line ◽

Glial Cell ◽

Hepatic Stellate Cell ◽

Neurotrophic Factor ◽

Cell Activation ◽

Stellate Cell ◽

Smad Signaling ◽

Hepatic Stellate Cell Activation

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Proteomic analysis of extracellular matrix from the hepatic stellate cell line LX-2 identifies CYR61 and Wnt-5a as novel constituents of fibrotic liver

Journal of Proteome Research ◽

10.1021/pr3000927 ◽

2012 ◽

Vol 11 (8) ◽

pp. 4052-4064 ◽

Cited By ~ 51

Author(s):

S. Tamir Rashid ◽

Jonathan D. Humphries ◽

Adam Byron ◽

Ameet Dhar ◽

Janet A. Askari ◽

...

Keyword(s):

Extracellular Matrix ◽

Cell Line ◽

Hepatic Stellate Cell ◽

Proteomic Analysis ◽

Stellate Cell ◽

Fibrotic Liver

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Activity and expression of ecto-5′-nucleotidase/CD73 are increased during phenotype conversion of a hepatic stellate cell line

Life Sciences ◽

10.1016/j.lfs.2007.10.003 ◽

2008 ◽

Vol 82 (1-2) ◽

pp. 21-29 ◽

Cited By ~ 15

Author(s):

Cláudia M.B. Andrade ◽

Gislaine C. Roesch ◽

Márcia R. Wink ◽

Eduardo L.M. Guimarães ◽

Luiz F. Souza ◽

...

Keyword(s):

Cell Line ◽

Hepatic Stellate Cell ◽

Stellate Cell

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Verrucosamide, a Cytotoxic 1,4-Thiazepane-Containing Thiodepsipeptide from a Marine-Derived Actinomycete

Marine Drugs ◽

10.3390/md18110549 ◽

2020 ◽

Vol 18 (11) ◽

pp. 549

Author(s):

Vimal Nair ◽

Min Cheol Kim ◽

James A. Golen ◽

Arnold L. Rheingold ◽

Gabriel A. Castro ◽

...

Keyword(s):

Breast Carcinoma ◽

Diffraction Study ◽

Cell Line ◽

Absolute Configuration ◽

Spectral Methods ◽

Biosynthetic Pathway ◽

Cyclic Peptide ◽

Colon Adenocarcinoma ◽

X Ray Diffraction ◽

X Ray

A new cytotoxic thiodepsipeptide, verrucosamide (1), was isolated along with the known, related cyclic peptide thiocoraline, from the extract of a marine-derived actinomycete, a Verrucosispora sp., our strain CNX-026. The new peptide, which is composed of two rare seven-membered 1,4-thiazepane rings, was elucidated by a combination of spectral methods and the absolute configuration was determined by a single X-ray diffraction study. Verrucosamide (1) showed moderate cytotoxicity and selectivity in the NCI 60 cell line bioassay. The most susceptible cell lines were MDA-MB-468 breast carcinoma with an LD50 of 1.26 µM, and COLO 205 colon adenocarcinoma with an LD50 of 1.4 µM. Also isolated along with verrucosamide were three small 3-hydroxy(alkoxy)-quinaldic acid derivatives that appear to be products of the same biosynthetic pathway.

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Establishment of an Immortalized Human Hepatic Stellate Cell Line to Develop Antifibrotic Therapies

Cell Transplantation ◽

10.3727/000000003108747064 ◽

2003 ◽

Vol 12 (5) ◽

pp. 499-507 ◽

Cited By ~ 36

Author(s):

Norikuni Shibata ◽

Takamasa Watanabe ◽

Teru Okitsu ◽

Masakiyo Sakaguchi ◽

Michihiko Takesue ◽

...

Keyword(s):

Cell Line ◽

Hepatic Stellate Cell ◽

Type I Collagen ◽

Replicative Senescence ◽

Stellate Cell ◽

Smooth Muscle Actin ◽

Population Doubling ◽

Type I ◽

Human Hepatic Stellate Cell ◽

Ifn Γ

Because human hepatic stellate cells (HSCs) perform a crucial role in the progress of hepatic fibrosis, it is of great value to establish an immortalized human cell line that exhibits HSC characteristics and grows well in tissue cultures for the development of antifibrotic therapies. Thus, we engineered an immortalized human hepatic stellate cell (HSC) line TWNT-4 by retrovirally inducing human telomerase reverse transcriptase (hTERT) into LI 90 cells established from a human liver mesenchymal tumor. Parental LI 90 entered replicative senescence, whereas TWNT-4 showed telomerase activity and proliferated for more than population doubling level (PDL) 200 without any crisis. TWNT-4 expressed platelet-derived growth factor-β receptor (PDGF-βR), α-smooth muscle actin (α-SMA), and type I collagen (α1) and was considered to be an activated form of HSCs. Treatment of TWNT-4 cells with either 100 U/ml of IFN-γ or 1 ng/ml of rapamycin (Rapa) for 14 days led to lower expression of type I collagen (α1) at RNA and protein levels. Exposure of TWNT-4 cells to both of IFN-γ (10 U/ml) and Rapa (0.1 ng/ml) for 14 days effectively decreased the expression of type I collagen (α1), PDGF-βR, and α-SMA expression and suppressed TGF-β1 secretion of TWNT-4 cells. We successfully induced apoptosis by transducing TNF-related apoptosis-inducing ligand (TRAIL) into TWNT-4 cells using adenovirus vectors Ad/GT-TRAIL and Ad/PGK-GV-17. These findings suggested that immortalized activated HSC line TWNT-4 would be a useful means to develop antifibrotic therapies.

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