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The Natural Product Parthenolide Inhibits Both Angiogenesis and Invasiveness and Improves Gemcitabine Resistance by
Yuki Denda1, Yoichi Matsuo1, Saburo Sugita1
1Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Nutrients
|March 13, 2024
Summary
Parthenolide effectively inhibits pancreatic cancer cell growth and reduces invasion by suppressing nuclear factor κB (NF-κB) activity. This compound also re-sensitizes gemcitabine-resistant pancreatic cancer to chemotherapy.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Pancreatic cancer (PaCa) often develops gemcitabine resistance.
- Nuclear factor κB (NF-κB) signaling is upregulated in gemcitabine-resistant PaCa.
- Parthenolide, from feverfew, has known antitumor properties via NF-κB inhibition.
Purpose of the Study:
- To investigate the efficacy of parthenolide against gemcitabine-resistant PaCa.
- To determine parthenolide's effect on NF-κB activity and related pathways in resistant PaCa.
- To assess parthenolide's potential to restore gemcitabine sensitivity.
Main Methods:
- Cell culture of gemcitabine-resistant and normal PaCa cells.
- Treatment with varying concentrations of parthenolide.
- Assays for cell proliferation, NF-κB activity, invasion, angiogenesis, and MRP1 expression.
- Colony formation assays to evaluate chemosensitivity.
Main Results:
- Parthenolide inhibited proliferation of both normal and resistant PaCa cells (≥10 µM).
- NF-κB activity was significantly inhibited by low parthenolide concentrations (≥1 µM).
- Parthenolide reduced invasion, angiogenesis, and MRP1 expression in resistant PaCa cells.
- Parthenolide (1 µM) enhanced gemcitabine sensitivity in resistant PaCa cells.
Conclusions:
- Parthenolide demonstrates significant antitumor activity against gemcitabine-resistant pancreatic cancer.
- Parthenolide effectively suppresses key pathways involved in pancreatic cancer resistance and metastasis.
- Parthenolide shows promise as a therapeutic agent to overcome gemcitabine resistance in pancreatic cancer.
