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 microM (2.5-10 micrograms/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 microM (2.5 micrograms/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 G2-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.
Lindenmeyer
F
F
Institut National de la Santé et de la Recherche Médicale, U553, Bât. INSERM, Institut d'Hématologie, Hôpital Saint-Louis, Université Paris 7, 75475 Paris, France.
Li
H
H
Menashi
S
S
Soria
C
C
Lu
H
H
D000970:Antineoplastic Agents / Q000494:pharmacology*; D047310:Apigenin; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D010450:Endopeptidases / Q000096:biosynthesis*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D000970:Antineoplastic Agents; D005419:Flavonoids; D047310:Apigenin; D010450:Endopeptidases; D014568:Urokinase-Type Plasminogen Activator; D020780:Matrix Metalloproteinase 9