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

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.

Proteomics Analysis for Identification of Potential Cell Signaling Pathways and Protein Targets of Actions of Atractylodin and β-Eudesmol Against Cholangiocarcinoma

“…Ursolic acid from Ligustrum lucidum and the chemotherapeutic drug cisplatin, have been shown to inhibit cervical cancer cell growth through interfering with NF-κB signaling pathway via decreasing p65 level (Li et al, 2017a). Xanthohumol from Humulus lupulus L. was also shown to inhibit pancreatic cancer cell angiogenesis through interfering with this pathway (Saito et al, 2017).…”

Xanthohumol, a Prenylated Flavonoid from Hops, Induces DNA Damages in Colorectal Cancer Cells and Sensitizes SW480 Cells to the SN38 Chemotherapeutic Agent

“…A number of recent reports have shown that Xn could exert anticancer activities against various cancers such as leukemia [18], hepatocellular carcinoma [19], breast cancer [20,21], prostate cancer [22], colon cancer [23], and ovarian cancer [24]. This anticancer activity involves pleiotropic action on various signaling pathways, such as mitogen-activated protein kinase (MAPK) [25], mitochondria-and Bcl-2-related proteins (intrinsic apoptosis pathway) and the ligation of death receptors belonging to the tumor necrosis factor (TNF)-receptor superfamily (extrinsic apoptosis pathways) [26], and angiogenesis inhibition via the nuclear factor kappa B (NF-κB) pathway [27].…”

Translational pancreatic cancer research: A comparative study on patient-derived xenograft models

“…The extension of the vascular network is fundamental to assess the response to the treatment of anti-tumour drugs. Multiple authors use a microvessel density analysis system by CD31 expression in pancreatic PDX similar to ours[ 5 , 33 , 34 ].…”