Details

Autor(en) / Beteiligte

• Viola, Katharina
• Kopf, Sabine
• Rarova, Lucie
• Jarukamjorn, Kanokwan
• Kretschy, Nicole
• Teichmann, Mathias
• Vonach, Caroline
• Atanasov, Atanas G.
• Giessrigl, Benedikt
• Huttary, Nicole
• Raab, Ingrid
• Krieger, Sigurd
• Strnad, Miroslav
• de Martin, Rainer
• Saiko, Philipp
• Szekeres, Thomas
• Knasmüller, Siegfried
• Dirsch, Verena M.
• Jäger, Walter
• Grusch, Michael
• Dolznig, Helmut
• Mikulits, Wolfgang
• Krupitza, Georg

Titel

Xanthohumol attenuates tumour cell-mediated breaching of the lymphendothelial barrier and prevents intravasation and metastasis

Ist Teil von

• Archives of toxicology, 2013-07, Vol.87 (7), p.1301-1312

Ort / Verlag

Berlin/Heidelberg: Springer-Verlag

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• Health beneficial effects of xanthohumol have been reported, and basic research provided evidence for anti-cancer effects. Furthermore, xanthohumol was shown to inhibit the migration of endothelial cells. Therefore, this study investigated the anti-metastatic potential of xanthohumol. MCF-7 breast cancer spheroids which are placed on lymphendothelial cells (LECs) induce “circular chemorepellent-induced defects” (CCIDs) in the LEC monolayer resembling gates for intravasating tumour bulks at an early step of lymph node colonisation. NF-κB reporter-, EROD-, SELE-, 12( S )-HETE- and adhesion assays were performed to investigate the anti-metastatic properties of xanthohumol. Western blot analyses were used to elucidate the mechanisms inhibiting CCID formation. Xanthohumol inhibited the activity of CYP, SELE and NF-kB and consequently, the formation of CCIDs at low micromolar concentrations. More specifically, xanthohumol affected ICAM-1 expression and adherence of MCF-7 cells to LECs, which is a prerequisite for CCID formation. Furthermore, markers of epithelial-to-mesenchymal transition (EMT) and of cell mobility such as paxillin, MCL2 and S100A4 were suppressed by xanthohumol. Xanthohumol attenuated tumour cell-mediated defects at the lymphendothelial barrier and inhibited EMT-like effects thereby providing a mechanistic explanation for the anti-intravasative/anti-metastatic properties of xanthohumol.