We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
The Natural Product Parthenolide Inhibits Both Angiogenesis and Invasiveness and Improves Gemcitabine Resistance by Suppressing Nuclear Factor κB Activation in Pancreatic Cancer Cell Lines.
- Authors
Denda, Yuki; Matsuo, Yoichi; Sugita, Saburo; Eguchi, Yuki; Nonoyama, Keisuke; Murase, Hiromichi; Kato, Tomokatsu; Imafuji, Hiroyuki; Saito, Kenta; Morimoto, Mamoru; Ogawa, Ryo; Takahashi, Hiroki; Mitsui, Akira; Kimura, Masahiro; Takiguchi, Shuji
- 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.
- Subjects
PHYTOTHERAPY; THERAPEUTIC use of antineoplastic agents; NF-kappa B; CANCER invasiveness; DRUG resistance in cancer cells; HYDROCARBONS; BIOLOGICAL products; CELLULAR signal transduction; DESCRIPTIVE statistics; PANCREATIC tumors; PLANT extracts; CELL lines; GEMCITABINE; FEVERFEW; WESTERN immunoblotting; PATHOLOGIC neovascularization; DATA analysis software
- Publication
Nutrients, 2024, Vol 16, Issue 5, p705
- ISSN
2072-6643
- Publication type
Article
- DOI
10.3390/nu16050705