Carnosol, a Natural Polyphenol, Inhibits Migration, Metastasis, and Tumor Growth of Breast Cancer via a ROS-Dependent Proteasome Degradation of STAT3
Identifieur interne : 000969 ( Main/Curation ); précédent : 000968; suivant : 000970Carnosol, a Natural Polyphenol, Inhibits Migration, Metastasis, and Tumor Growth of Breast Cancer via a ROS-Dependent Proteasome Degradation of STAT3
Auteurs : Halima Alsamri [Émirats arabes unis] ; Hussain El Hasasna [Émirats arabes unis] ; Yusra Al Dhaheri [Émirats arabes unis] ; Ali H. Eid [Liban] ; Samir Attoub [Émirats arabes unis] ; Rabah Iratni [Émirats arabes unis]Source :
- Frontiers in Oncology [ 2234-943X ] ; 2019.
Abstract
We have previously demonstrated that carnosol, a naturally occurring diterpene, inhibited
Url:
DOI: 10.3389/fonc.2019.00743
PubMed: 31456939
PubMed Central: 6698796
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PMC:6698796Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Carnosol, a Natural Polyphenol, Inhibits Migration, Metastasis, and Tumor Growth of Breast Cancer via a ROS-Dependent Proteasome Degradation of STAT3</title>
<author><name sortKey="Alsamri, Halima" sort="Alsamri, Halima" uniqKey="Alsamri H" first="Halima" last="Alsamri">Halima Alsamri</name>
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<author><name sortKey="Eid, Ali H" sort="Eid, Ali H" uniqKey="Eid A" first="Ali H." last="Eid">Ali H. Eid</name>
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<author><name sortKey="Attoub, Samir" sort="Attoub, Samir" uniqKey="Attoub S" first="Samir" last="Attoub">Samir Attoub</name>
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<author><name sortKey="Iratni, Rabah" sort="Iratni, Rabah" uniqKey="Iratni R" first="Rabah" last="Iratni">Rabah Iratni</name>
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<series><title level="j">Frontiers in Oncology</title>
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<front><div type="abstract" xml:lang="en"><p>We have previously demonstrated that carnosol, a naturally occurring diterpene, inhibited <italic>in vitro</italic>
cell viability and colony growth, as well as induced cell cycle arrest, autophagy and apoptosis in human triple negative breast cancer (TNBC) cells. In the present study, we evaluated the ability of carnosol to inhibit tumor growth and metastasis <italic>in vivo</italic>
. We found that non-cytotoxic concentrations of carnosol inhibited the migration and invasion of MDA-MB-231 cells in wound healing and matrigel invasion assays. Furthermore, gelatin zymography, ELISA, and RT-PCR assays revealed that carnosol inhibited the activity and downregulation the expression of MMP-9. Mechanistically, we demonstrated that carnosol suppressed the activation of STAT3 signaling pathway through a ROS-dependent targeting of STAT3 to proteasome-degradation in breast cancer cells (MDA-MB-231, Hs578T, MCF-7, and T47D). We show that blockade of proteasome activity, by MG-132 and bortezomib, or ROS accumulation, by N-acetylcysteine (NAC), restored the level of STAT3 protein. In addition, using chick embryo tumor growth assay, we showed that carnosol significantly and markedly suppressed tumor growth and metastasis of breast cancer xenografts. To the best of our knowledge, this is the first report which shows that carnosol specifically targets signal transducer and activator of transcription 3 (STAT3) for proteasome degradation in breast cancer. Our study further provide evidence that carnosol may represent a promising therapeutic candidate that canmodulate breast cancer growth and metastasis.</p>
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