Effect of catechins and citrus flavonoids on invasionin vitro

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Abstract
Catechins, a group of flavonoid molecules, inhibit invasion of mouse MO4 cells into embryonic chick heart fragmentsin vitro. The anti-invasive effects can be ranked as follows: (+)-catechin > (−)-epicatechin>3-O-methyl-(+)-catechin > 3-O-palmitoyl-(+)-catechin. Most of the catechins are unstable in cell culture media, and their spontaneous rearrangement products tend to bind to extracellular matrix (ECM). Due to these interactions proteases such as tissue-type plasminogen activator (t-PA) are linked to the ECM glycoprotein laminin. This leads to a partial inactivation of the enzyme. Within the group of catechins we found a positive correlation between anti-invasive activity and linking of t-PA to laminin. Citrus flavonoids are also anti-invasivein vitro (tangeretin > nobiletin > hesperidin = naringin). However, these stable molecules show poor affinity for ECM, and do not link enzymes to laminin. These data suggest that catechins and citrus flavonoids inhibit invasionin vitro by different mechanisms.