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Hesperetin, a bioflavonoid, inhibits rat aortic vascular smooth muscle cells proliferation by arresting cell cycle
Author(s) -
Jin YongRi,
Han XiangHua,
Zhang YongHe,
Lee JungJin,
Lim Yong,
Kim TackJoong,
Yoo HwanSoo,
Yun YeoPyo
Publication year - 2007
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21592
Subject(s) - hesperetin , cell cycle , platelet derived growth factor receptor , cyclin a , cell growth , microbiology and biotechnology , cyclin d , protein kinase b , vascular smooth muscle , chemistry , cyclin d1 , cyclin e , cancer research , cyclin dependent kinase 2 , kinase , biology , phosphorylation , protein kinase a , cell , endocrinology , growth factor , biochemistry , receptor , flavonoid , smooth muscle , antioxidant
Diet can be one of the most important factors that influence risks for cardiovascular diseases. Hesperetin, a flavonoid present in grapefruits and oranges, is one candidate that may benefit the cardiovascular system. In this study, we have investigated the effect of hesperetin on the platelet‐derived growth factor (PDGF)‐BB‐induced proliferation of primary cultured rat aortic vascular smooth muscle cells (VSMCs). Hesperetin significantly inhibited 50 ng/ml PDGF‐BB‐induced rat aortic VSMCs proliferation and [ 3 H]‐thymidine incorporation into DNA at concentrations of 5, 25, 50, and 100 µM. In accordance with these findings, hesperetin revealed blocking of the PDGF‐BB‐inducible progression through G 0 /G 1 to S phase of the cell cycle in synchronized cells. Western blot showed that hesperetin inhibited not only phosphorylation of retinoblastoma protein (pRb) and expressions of cyclin A, cyclin D, cyclin E, cyclin‐dependent kinase 2 (CDK2) as well as proliferating cell nuclear antigen (PCNA) protein, but also downregulation of cyclin‐dependent kinase inhibitor (CKI) p27 kip1 , while did not affect CKI p21 cip1 , p16 INK4 , p53, and CDK4 expressions as well as early signaling transductions such as PDGF beta‐receptor, extracellular signal‐regulated kinase (ERK) 1/2, Akt, p38, and JNK phosphorylation. These results suggest that hesperetin inhibits PDGF‐BB‐induced rat aortic VSMCs proliferation via G 0 /G 1 arrest in association with modulation of the expression or activation of cell‐cycle regulatory proteins, which may contribute to the beneficial effect of grapefruits and oranges on cardiovascular system. J. Cell. Biochem. 104: 1–14, 2008. © 2007 Wiley‐Liss, Inc.