The fungal secondary metabolite trichodimerol inhibits TGF-β dependent cellular effects and tube formation of MDA-MB-231 cells
The transforming growth factor-beta (TGF-beta) family of ligands has a pivotal role as regulators of cell growth, differentiation and migration. Overexpression of TGF-beta has been associated with breast, colon, hepatocellular, lung and pancreatic cancer. Importantly, overexpression of TGF-beta correlates with tumor progression, metastasis, angiogenesis and poor prognostic outcome. Therefore, TGF-beta signaling has emerged as an attractive target for the development of new cancer therapeutics. In a search for metabolites from fungi inhibiting the TGF-beta dependent expression of a reporter gene in HepG2 cells, we found that trichodimerol, a previously isolated bisorbicillinoid, inhibited serine phosphorylation of the TGF-beta activated Smad2/3 transcription factors and antagonized the cellular effects of TGF-beta including reporter gene activation and expression of TGF-beta inducible genes in HepG2 and MDA-MB-231 cells. In addition, trichodimerol blocked IFN-gamma, IL-6 and IL-4 induced activation of Stat1, Stat3 and Stat6 transcription factors by inhibiting serine and tyrosine phosphorylation. In an in vitro angiogenesis assay, 20 muM trichodimerol completely abrogated the capillary-like tube formation of MDA-MB-231 cells on Matrigel.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2009 |
---|---|
Erschienen: |
2009 |
Enthalten in: |
Zur Gesamtaufnahme - volume:27 |
---|---|
Enthalten in: |
Investigational new drugs - 27(2009), 6 vom: 30. Dez., Seite 491-502 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Serwe, Annegret [VerfasserIn] |
---|
Links: |
---|
Anmerkungen: |
Date Completed 19.04.2013 Date Revised 20.10.2021 published: Print-Electronic Citation Status MEDLINE |
---|
doi: |
10.1007/s10637-008-9201-9 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM184493781 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM184493781 | ||
003 | DE-627 | ||
005 | 20231223170735.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231223s2009 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1007/s10637-008-9201-9 |2 doi | |
028 | 5 | 2 | |a pubmed24n0615.xml |
035 | |a (DE-627)NLM184493781 | ||
035 | |a (NLM)19009233 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Serwe, Annegret |e verfasserin |4 aut | |
245 | 1 | 4 | |a The fungal secondary metabolite trichodimerol inhibits TGF-β dependent cellular effects and tube formation of MDA-MB-231 cells |
264 | 1 | |c 2009 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 19.04.2013 | ||
500 | |a Date Revised 20.10.2021 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a The transforming growth factor-beta (TGF-beta) family of ligands has a pivotal role as regulators of cell growth, differentiation and migration. Overexpression of TGF-beta has been associated with breast, colon, hepatocellular, lung and pancreatic cancer. Importantly, overexpression of TGF-beta correlates with tumor progression, metastasis, angiogenesis and poor prognostic outcome. Therefore, TGF-beta signaling has emerged as an attractive target for the development of new cancer therapeutics. In a search for metabolites from fungi inhibiting the TGF-beta dependent expression of a reporter gene in HepG2 cells, we found that trichodimerol, a previously isolated bisorbicillinoid, inhibited serine phosphorylation of the TGF-beta activated Smad2/3 transcription factors and antagonized the cellular effects of TGF-beta including reporter gene activation and expression of TGF-beta inducible genes in HepG2 and MDA-MB-231 cells. In addition, trichodimerol blocked IFN-gamma, IL-6 and IL-4 induced activation of Stat1, Stat3 and Stat6 transcription factors by inhibiting serine and tyrosine phosphorylation. In an in vitro angiogenesis assay, 20 muM trichodimerol completely abrogated the capillary-like tube formation of MDA-MB-231 cells on Matrigel | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 7 | |a Bridged-Ring Compounds |2 NLM | |
650 | 7 | |a Hypoxia-Inducible Factor 1, alpha Subunit |2 NLM | |
650 | 7 | |a RNA, Messenger |2 NLM | |
650 | 7 | |a STAT Transcription Factors |2 NLM | |
650 | 7 | |a Transforming Growth Factor beta |2 NLM | |
650 | 7 | |a trichodimerol |2 NLM | |
650 | 7 | |a Janus Kinases |2 NLM | |
650 | 7 | |a EC 2.7.10.2 |2 NLM | |
700 | 1 | |a Anke, Timm |e verfasserin |4 aut | |
700 | 1 | |a Erkel, Gerhard |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Investigational new drugs |d 1993 |g 27(2009), 6 vom: 30. Dez., Seite 491-502 |w (DE-627)NLM013000160 |x 1573-0646 |7 nnns |
773 | 1 | 8 | |g volume:27 |g year:2009 |g number:6 |g day:30 |g month:12 |g pages:491-502 |
856 | 4 | 0 | |u http://dx.doi.org/10.1007/s10637-008-9201-9 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 27 |j 2009 |e 6 |b 30 |c 12 |h 491-502 |