Premium
Apigenin inhibits endothelial‐cell proliferation in G 2 /M phase whereas it stimulates smooth‐muscle cells by inhibiting P21 and P27 expression
Author(s) -
Trochon Véronique,
Blot Emmanuel,
Cymbalista Florence,
Engelmann Carsten,
Tang RuoPing,
Thomaïdis Annick,
Vasse Marc,
Soria Jeannette,
Lu He,
Soria Claudine
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(20000301)85:5<691::aid-ijc15>3.0.co;2-q
Subject(s) - apigenin , cell growth , microbiology and biotechnology , angiogenesis , vascular smooth muscle , chemistry , endothelial stem cell , cell cycle , cyclin a , biology , in vitro , cell , cancer research , biochemistry , cyclin d1 , flavonoid , endocrinology , smooth muscle , antioxidant
Abstract Apigenin is a plant flavonoid that is thought to play a role in the prevention of carcinogenesis. However, its mechanism of action has not yet been elucidated. Because of the importance of angiogenesis in tumor growth, we investigated the effect of apigenin on endothelial and smooth‐muscle cells in an in vitro model. Apigenin markedly inhibited the proliferation, and, to a lesser degree, the migration of endothelial cells, and capillary formation in vitro, independently of its inhibition of hyaluronidase activity. In contrast, it strongly stimulated vascular smooth‐muscle‐cell proliferation. The molecular mechanisms of apigenin activity were analyzed in these 2 types of cells. Our results show that apigenin inhibits endothelial‐cell proliferation by blocking the cells in the G 2 /M phase as a result of the accumulation of the hyperphosphorylated form of the retinoblastoma protein. Apigenin stimulation of smooth‐muscle cells was attributed to the reduced expression of 2 cyclin‐dependent kinase inhibitors, p21 and p27, which negatively regulate the G 1 ‐phase cyclin‐dependent kinase. Int. J. Cancer 85:691–696, 2000. © 2000 Wiley‐Liss, Inc.