interleukin-8 and xanthohumol

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.

Topics: Angiogenesis Inhibitors; Animals; Cell Line, Tumor; Cell Proliferation; Cell Survival; Coculture Techniques; Flavonoids; Gene Expression Regulation, Neoplastic; Humans; Interleukin-8; Mice; Pancreatic Neoplasms; Propiophenones; Transcription Factor RelA; Vascular Endothelial Growth Factor A; Xenograft Model Antitumor Assays

Xanthohumol, the major prenylated chalcone found in hops, is well known to exert anti-cancer effects, but information regarding the impact on hepatocellular carcinoma (HCC) cells and potential adverse effects on non-tumorous hepatocytes is limited. Here, we show that xanthohumol at a concentration of 25 microM induced apoptosis in two HCC cell lines (HepG2 and Huh7). Furthermore, xanthohumol repressed proliferation and migration, as well as TNF induced NF-kappaB activity and interleukin-8 expression in both cell lines at even lower concentrations. In contrast, xanthohumol concentrations up to 100 microM did not affect viability of primary human hepatocytes in vitro. In summary, our data showed that xanthohumol can ameliorate different pro-tumorigenic mechanisms known to promote HCC progression, indicating its potential as promising therapeutic agent that selectively affects cancer cells.

Topics: Antineoplastic Agents; Apoptosis; Carcinoma, Hepatocellular; Cell Movement; Cell Proliferation; Cell Survival; Flavonoids; Humans; Humulus; Interleukin-8; Liver Neoplasms; Propiophenones; Reverse Transcriptase Polymerase Chain Reaction