Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
The sesquiterpene lactone parthenolide in combination with docetaxel reduces metastasis and improves survival in a xenograft model of breast cancer
Ist Teil von
Molecular cancer therapeutics, 2005-06, Vol.4 (6), p.1004-1012
Ort / Verlag
United States: American Association for Cancer Research
Erscheinungsjahr
2005
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
Parthenolide, a sesquiterpene lactone, shows antitumor activity in vitro , which correlates with its ability to inhibit the DNA binding of the antiapoptotic transcription factor nuclear factor κB
(NF-κB) and activation of the c-Jun NH 2 -terminal kinase. In this study, we investigated the chemosensitizing activity of parthenolide in vitro as well as in MDA-MB-231 cell–derived xenograft metastasis model of breast cancer. HBL-100 and MDA-MB-231 cells were used
to measure the antitumor and chemosensitizing activity of parthenolide in vitro . Parthenolide was effective either alone or in combination with docetaxel in reducing colony formation, inducing apoptosis
and reducing the expression of prometastatic genes IL-8 and the antiapoptotic gene GADD45β1 in vitro . In an adjuvant setting, animals treated with parthenolide and docetaxel combination showed significantly enhanced survival
compared with untreated animals or animals treated with either drug. The enhanced survival in the combination arm was associated
with reduced lung metastases. In addition, nuclear NF-κB levels were lower in residual tumors and lung metastasis of animals
treated with parthenolide, docetaxel, or both. In the established orthotopic model, there was a trend toward slower growth
in the parthenolide-treated animals but no statistically significant findings were seen. These results for the first time
reveal the significant in vivo chemosensitizing properties of parthenolide in the metastatic breast cancer setting and support the contention that metastases
are very reliant on activation of NF-κB.