Effect of catechins and citrus flavonoids on invasion in vitro.

Catechins, a group of flavonoid molecules, inhibit invasion of mouse MO4 cells into embryonic chick heart fragments in vitro. The anti-invasive effects can be ranked as follows: (+)-catechin greater than (-)-epicatechin greater than 3-O-methyl-(+)-catechin greater than 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-invasive in vitro (tangeretin greater than nobiletin greater than 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 invasion in vitro by different mechanisms.