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Verfasst von:Rasheed, Suhail Ahmed Kabeer [VerfasserIn]   i
 Efferth, Thomas [VerfasserIn]   i
 Asangani, Irfan A. [VerfasserIn]   i
 Allgayer, Heike [VerfasserIn]   i
Titel:First evidence that the antimalarial drug artesunate inhibits invasion and in vivo metastasis in lung cancer by targeting essential extracellular proteases
Verf.angabe:Suhail Ahmed Kabeer Rasheed, Thomas Efferth, Irfan Ahmed Asangani and Heike Allgayer
E-Jahr:2010
Jahr:19 July 2010
Umfang:11 S.
Fussnoten:Gesehen am 10.05.2023
Titel Quelle:Enthalten in: International journal of cancer
Ort Quelle:Bognor Regis : Wiley-Liss, 1966
Jahr Quelle:2010
Band/Heft Quelle:127(2010), 6 vom: Juli, Seite 1475-1485
ISSN Quelle:1097-0215
Abstract:Despite progress in treatment, progressive non-small cell lung cancer (NSCLC) still limits survival dramatically, and novel therapeutic compounds are needed. Initial investigations suggest that artesunate (ART), an antimalarial drug, has antiproliferative capacities. However, antiinvasive and antimetastatic properties of ART in cancer have never been explored. Therefore, this first study was performed to (i) investigate if ART is able to inhibit invasion and metastasis in NSCLC and (ii) to identify first molecular targets and mechanisms mediating this ability. ART significantly impaired matrigel invasion of 6 NSCLC cell lines and inhibited urokinase-type plasminogen activator (u-PA) activity, -protein and -mRNA expression. Furthermore, in a PCR-metastasis array, ART inhibited the expression of several matrix metalloproteinases (MMPs), especially MMP-2 and MMP-7 mRNA/protein. In luciferase reporter assays, ART downregulated MMP-2-, MMP-7- and u-PA-promoter/-enhancer activity, in parallel to AP-1- and NF-kB-transactivation. Si-RNA knockdown of u-PA, MMP-2 and MMP-7 abolished ART's ability to inhibit invasion, confirming their role as essential mediators. In vivo, ART significantly impaired primary tumor growth and metastasis in the chicken embryo metastasis (CAM) model. In conclusion, this is the first study to show that ART considerably suppresses invasion and metastasis in NSCLC, specifically targeting transcription of u-PA, MMP-2 and MMP-7, prompting immediate studies on ART as a novel therapeutic in NSCLC.
DOI:doi:10.1002/ijc.25315
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1002/ijc.25315
 Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.25315
 DOI: https://doi.org/10.1002/ijc.25315
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:artesunate
 metastasis
 non-small cell lung cancer
K10plus-PPN:1844975339
Verknüpfungen:→ Zeitschrift

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