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Published on: July 20, 2019
Xanthohumol inhibits angiogenesis by suppressing nuclear factor-κB activation in pancreatic cancer
Kenta Saito1, Yoichi Matsuo1, Hiroyuki Imafuji1
1Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
Abstract:
Xantohumol, a prenylated chalcone from hops (Humulus lupulus L.), has been shown to inhibit proliferation in some cancers. However, little is known regarding the effects of xanthohumol in pancreatic cancer. We have previously reported that activation of the transcription factor nuclear factor-κB (NF-κB) plays a key role in angiogenesis in pancreatic cancer. In this study, we investigated whether xanthohumol inhibited angiogenesis by blocking NF-κB activation in pancreatic cancer in vitro and in vivo. We initially confirmed that xanthohumol significantly inhibited proliferation and NF-κB activation in pancreatic cancer cell lines. Next, we demonstrated that xanthohumol significantly suppressed the expression of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) at both the mRNA and protein levels in pancreatic cancer cell lines. We also found that coculture with BxPC-3 cells significantly enhanced tube formation in human umbilical vein endothelial cells, and treatment with xanthohumol significantly blocked this effect. In vivo, the volume of BxPC-3 subcutaneous xenograft tumors was significantly reduced in mice treated with weekly intraperitoneal injections of xanthohumol. Immunohistochemistry revealed that xanthohumol inhibited Ki-67 expression, CD31-positive microvessel density, NF-κB p65 expression, and VEGF and IL-8 levels. Taken together, these results showed, for the first time, that xanthohumol inhibited angiogenesis by suppressing NF-κB activity in pancreatic cancer. Accordingly, xanthohumol may represent a novel therapeutic agent for the management of pancreatic cancer.
Insights
Xanthohumol, a compound from hops, inhibits pancreatic cancer growth and angiogenesis by blocking nuclear factor-kappa B (NF-κB) activation. This suggests xanthohumol
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Pancreatic cancer is a leading cause of cancer death with limited treatment options.
- Nuclear factor-kappa B (NF-κB) activation is crucial for pancreatic cancer angiogenesis.
- Xanthohumol, a hop-derived chalcone, shows anti-cancer properties but its role in pancreatic cancer is unclear.
Purpose of the Study:
- To investigate the anti-angiogenic effects of xanthohumol in pancreatic cancer.
- To determine if xanthohumol inhibits pancreatic cancer by blocking NF-κB activation.
- To evaluate xanthohumol's efficacy in vitro and in vivo.
Main Methods:
- In vitro studies using pancreatic cancer cell lines (proliferation, NF-κB activation, VEGF, IL-8 expression).
- Endothelial cell tube formation assays.
- In vivo studies using xenograft mouse models (tumor volume, immunohistochemistry for Ki-67, CD31, NF-κB p65, VEGF, IL-8).
Main Results:
- Xanthohumol significantly inhibited pancreatic cancer cell proliferation and NF-κB activation.
- Xanthohumol suppressed vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) expression.
- Xanthohumol reduced angiogenesis in vitro and in vivo, decreasing microvessel density and tumor growth.
Conclusions:
- Xanthohumol inhibits pancreatic cancer angiogenesis by suppressing NF-κB activity.
- Xanthohumol demonstrates therapeutic potential for pancreatic cancer treatment.
- Further research into xanthohumol as a novel pancreatic cancer therapeutic agent is warranted.
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