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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 Bx PC ‐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 Bx PC ‐3 subcutaneous xenograft tumors was significantly reduced in mice treated with weekly intraperitoneal injections of xanthohumol. Immunohistochemistry revealed that xanthohumol inhibited Ki‐67 expression,  CD 31‐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.

Xanthohumol inhibits angiogenesis by suppressing nuclear factor‐κB activation in pancreatic cancer