Apigenin acts on the tumor cell invasion process and regulates protease production

Apigenin is a widely distributed plant flavonoid and was proposed as an antitumor agent. In this study, we investigated the apigenin effects on the protease-mediated invasiveness in an estrogen-insensitive breast tumor cell line MDA-MB231. The results show that apigenin at 22.8-45.5 muM (2.5-10 mug/ml) strongly inhibited, in a dose-dependent manner, tumor cell invasion through Matrigel, cell migration, and cell proliferation. We show that apigenin treatment from 22.8 muM (2.5 mug/ml) led to a partial decrease in urokinase-plasminogen activator expression and to a total inhibition of phorbol 12-myristate 13-acetate-induced matrix metalloproteinase-9 secretion. We also demonstrate in the apigenin-treated cells a defective adhesion to Matrigel and a G(2)-M cell cycle arrest. Taken together, our results demonstrate that apigenin is a pleiotropic effector affecting protease-dependent invasiveness and associated processes and proliferation of tumor cells.