Flavonoid apigenin inhibits motility and invasiveness of carcinoma cells in vitro.

Investigations of the mechanisms of the cancer-preventive activity of apigenin (4',5,7,-trihydroxyflavone), a plant-derived, anti-carcinogenic flavonoid, showed its interference with cell proliferation, survival, and gap junctional coupling. We used a model based on non-invasive HeLa wild-type cells and their connexin43 (Cx43) transfected counterparts to correlate the effect of apigenin on tumour cell invasiveness with its influence on cell motility. Both cell lines displayed similar motile properties in control conditions. Apigenin treatment resulted in a significant and reversible inhibition of translocation of both HeLa wild-type cells and HeLa Cx43 transfectants. The effect of apigenin on cell proliferation was less pronounced especially at low apigenin concentration, whereas its influence on cell motility correlated with the reduction of the invasive potential of HeLa Cx43 cells as shown by an invasion assay based on the confrontation of tumour cell spheroids with chick embryo heart fragments. HeLa Cx43 cells were highly invasive in controls, but did not invade the heart tissue at tumour cell aggregate-fibroblast capsule interfaces in the presence of apigenin and failed to fully engulf these heart fragments. Because the motility of chick heart fibroblasts was only slightly affected by apigenin, these observations indicate that apigenin exerts its anti-invasive effect on HeLa cells predominantly via a specific inhibition of tumour cell motility. This inhibitory effect of apigenin on tumour cell invasiveness in vitro demonstrates that apigenin may exert its anti-tumorigenic effect in vivo via inhibition of tumour cell penetration of the healthy tissue.