The Natural Product Parthenolide Inhibits Both Angiogenesis and Invasiveness and Improves Gemcitabine Resistance by Suppressing Nuclear Factor κB Activation in Pancreatic Cancer Cell Lines.
Nutrients
; 16(5)2024 Feb 29.
Article
em En
| MEDLINE
| ID: mdl-38474833
ABSTRACT
We previously established pancreatic cancer (PaCa) cell lines resistant to gemcitabine and found that the activity of nuclear factor κB (NF-κB) was enhanced upon the acquisition of gemcitabine resistance. Parthenolide, the main active ingredient in feverfew, has been reported to exhibit antitumor activity by suppressing the NF-κB signaling pathway in several types of cancers. However, the antitumor effect of parthenolide on gemcitabine-resistant PaCa has not been elucidated. Here, we confirmed that parthenolide significantly inhibits the proliferation of both gemcitabine-resistant and normal PaCa cells at concentrations of 10 µM and higher, and that the NF-κB activity is significantly inhibited, even by 1 µM parthenolide. In Matrigel invasion assays and angiogenesis assays, the invasive and angiogenic potentials were higher in gemcitabine-resistant than normal PaCa cells and were inhibited by a low concentration of parthenolide. Furthermore, Western blotting showed suppressed MRP1 expression in gemcitabine-resistant PaCa treated with a low parthenolide concentration. In a colony formation assay, the addition of 1 µM parthenolide improved the sensitivity of gemcitabine-resistant PaCa cell lines to gemcitabine. These results suggest that parthenolide may be used as a novel therapeutic agent for the treatment of gemcitabine-resistant PaCa.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Sesquiterpenos
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Gencitabina
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article