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Abstract Title:

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

Abstract Source:

Arch Toxicol. 2013 Jul ;87(7):1301-12. Epub 2013 Mar 17. PMID: 23503627

Abstract Author(s):

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

Article Affiliation:

Katharina Viola

Abstract:

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.

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