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Zerumbone inhibits angiogenesis by blocking NF-κB activity in pancreatic cancer
Tomoya Shamoto1, Yoichi Matsuo, Takahiro Shibata
1From the Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Objectives:
Because angiogenesis is essential for tumor growth and metastasis, the development of antiangiogenic agents is an urgent issue in cancer treatment. Zerumbone, a component of subtropical ginger, has been shown to exhibit anticancer activities in various cancer cells; however, little is known about its biological mechanisms against angiogenesis in pancreatic cancer (PaCa). Here, we evaluated the effects of zerumbone on PaCa angiogenesis.
Methods:
The cytotoxicity of zerumbone in PaCa was measured using premix WST-1 cell proliferation assays. The influence of zerumbone on the angiogenic factors vascular endothelial growth factor and interleukin 8 was measured using the reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assays. Changes in nuclear factor-κB (NF-κB) activities were measured using NF-κB transcription factor assays. We also examined the effects of zerumbone on PaCa-induced angiogenesis using angiogenesis assays.
Results:
Zerumbone inhibited mRNA expression and protein secretion of angiogenic factors and NF-κB activity. Tube formation in human umbilical vein endothelial cells was enhanced by coculture with PaCa cells, and these enhancements were significantly inhibited by zerumbone treatment.
Conclusions:
Zerumbone blocked the PaCa-associated angiogenesis through the inhibition of NF-κB and NF-κB-dependent proangiogenic gene products.
Insights
Zerumbone, found in ginger, inhibits pancreatic cancer growth by blocking blood vessel formation. This natural compound targets key pathways, offering a potential new strategy for pancreatic cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Natural Products Chemistry
Background:
- Angiogenesis is crucial for tumor growth and metastasis, making antiangiogenic therapies a priority in cancer treatment.
- Zerumbone, a natural compound from ginger, demonstrates anticancer properties, but its antiangiogenic mechanisms in pancreatic cancer remain unclear.
- Pancreatic cancer (PaCa) requires effective therapeutic strategies, highlighting the need to investigate novel agents like zerumbone.
Purpose of the Study:
- To investigate the antiangiogenic effects of zerumbone on pancreatic cancer.
- To elucidate the molecular mechanisms by which zerumbone affects angiogenesis in pancreatic cancer.
- To evaluate zerumbone's potential as an antiangiogenic agent for pancreatic cancer therapy.
Main Methods:
- Cytotoxicity of zerumbone assessed using WST-1 assays.
- Expression and secretion of vascular endothelial growth factor and interleukin 8 measured via RT-PCR and ELISA.
- Nuclear factor-kappa B (NF-κB) activity and PaCa-induced angiogenesis evaluated using transcription factor and angiogenesis assays.
Main Results:
- Zerumbone significantly reduced mRNA and protein levels of proangiogenic factors.
- NF-κB activity was inhibited by zerumbone treatment.
- Zerumbone suppressed PaCa cell-induced tube formation in human umbilical vein endothelial cells.
Conclusions:
- Zerumbone effectively inhibits pancreatic cancer-associated angiogenesis.
- The antiangiogenic effect is mediated by the suppression of NF-κB signaling pathway.
- Zerumbone blocks NF-κB-dependent proangiogenic gene products, suggesting its therapeutic potential.
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