Effect of catechins and citrus flavonoids on invasionin vitro

Abstract

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.

Phytophenolic Nutrients in Citrus: Biochemical and Molecular Evidence

“…For example, quercetin prominently enhances the effect of Adriamycin in a multidrug-resistant MCF-7 human breast cancer cell line (Scambia et al 1994) and cells of colon MCT-15 (Critch fi eld et al 1994 ) . The anti-metastatic and anti-invasive activities of citrus fl avonoids, based on cell mobility inhibition (Bracke et al 1991 ) , have been observed in several human neoplastic cellular line proliferations: lymphoid and myeloid leukaemias (Larocca et al 1990 ) , gastric carcinoma (Yoshida et al 1990 ) , ovarian carcinoma (Scambia et al 1990 ) , prostate carcinoma (Peterson and Barnes 1993 ) and squamous cellular carcinoma (Kandaswami et al 1991 ) .…”

Flavonoids: Promising anticancer agents

“…76 A polymethoxy flavonoid, nobiletin, from Citrus depressa inhibited the tumor-invasive activity of human fibrosarcoma HT-1080 cells in the Matrigel model, which was likely through suppressing the expression of matrix metalloproteases (MMPs) and augmenting of tissue inhibitors of metalloproteinases (TIMPs) production in tumor cells. 77 When given i.p., quercetin and apigenin inhibited melanoma cell (B16-BL6) growth and metastatic potential in syngenetic mice, and interestingly, they significantly decreased the invasion of B16-BL6 cells in vitro.…”

Flavonoids, a ubiquitous dietary phenolic subclass, exert extensive in vitro anti-invasive and in vivo anti-metastatic activities

“…Tangeretin has been investigated for its antiproliferative [194] and anti-invasive properties [195,196]. In breast cancer, tangeretin upregulated the function of the Ecadherin/catenin complex in MCF-7/6 cells, which consequently led to firm cell-cell adhesions and inhibited cell invasion [197].…”