Structural Insight into the In Vitro Anti-Intravasative Properties of Flavonoids

Abstract

We investigated the effect of 21 flavonoids in a three-dimensional in vitro system for their ability to inhibit gap formation by MCF-7 breast cancer spheroids in monolayers of lymphendothelial cells. Different representatives of the classes of flavones, flavonols, and flavanones were tested in the circular chemorepellent-induced defects (CCID)-assay. Bay11-7082, a known inhibitor of CCID formation served as the positive control. This study provides the first comparison of the potential of flavonoids to suppress features influencing the intravasation of MCF-7 breast cancer cells aggregates through the lymph endothelial barrier. The most significant effects were seen after incubation with the flavones luteolin, chrysin, and apigenin. Additional hydroxylation or methoxylation in positions 6 or 8, as expected, resulted in decreased activity. The tested flavanones remained without or low efficacy.

Galenia africana plant extract exhibits cytotoxicity in breast cancer cells by inducing multiple programmed cell death pathways

“…2 B). These results are consistent with reports that the flavonoid Luteolin inhibited invasion of MDA-MB-231 cells by upregulating E-cadherin and downregulating the mesenchymal markers vimentin, N-cadherin, SNAIL and SLUG ( Eichsteininger et al, 2019 ). Together, the data showed that KB2 exhibited several anti-breast cancer properties.…”

Flavonoids Distinctly Stabilize Lymph Endothelial- or Blood Endothelial Disintegration Induced by Colon Cancer Spheroids SW620

“…Consistent with earlier results in a MCF7/LEC model [ 6 ], the 2-phenyl-5,7-dihydroxy-chromen-4-one structure of flavones without any additional substitution in positions 6 or 8 seems essential for the effects in all three 3D models and the IC 50 values of the most active substances apigenin, acacetin, luteolin and chrysin were in a comparable dimension.…”

“…In an earlier study, flavanones remained without any effects in a similar CCID model for breast cancer based on MCF7/LEC cells [ 6 ]. Surprisingly, in the here presented colon cancer models, the flavanone pinocembrin was weakly active in the LEC model and, although categorized as inactive, showed an IC 50 of 78.3 µM in the BEC model ( Supplemental Table S1 ).…”

“…No correlation between the activities in both CCID models and the logP values of the compounds was seen [ 6 ].…”

“…The promising activity of this extract was based on the flavonoid hispidulin and other unidentified components [ 5 ]. However, the concentration which inhibited 50% of circular chemorepellent induced defects (CCIDs) formation (IC 50 ) of hispidulin still was to high (~89 µM; [ 6 ]) to be considered for therapeutic concepts combating the spreading of breast cancer cells. Here we extended the approach and tested hispidulin and a panel of other structurally related flavonoids in colon cancer models, as orally taken compounds may get directly in contact with the colon epithelium.…”