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Articles

Genistein, Daidzein and Glycitein Inhibit Growth and DNA Synthesis of Aortic Smooth Muscle Cells from Stroke-Prone Spontaneously Hypertensive Rats

Weijun Pan^*,1, Katsumi Ikeda^*, Minoru Takebe and Yukio Yamori^*

^* Department of Environmental Preservation and Development, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto 606-8501 and Biotics Department, Nichimo Company, Tokyo 140-0002, Japan

¹To whom correspondence should be addressed. E-mail: weijun_pan{at}nichimo.co.jp.

Recent studies have reported that estrogen replacement therapy (ERT) reduces the risk of cardiovascular diseases in postmenopausal women. However, mechanisms responsible for this effect are not yet completely understood, and ERT is associated with carcinogenic side effects in women and feminizing effects in men. Because soybean isoflavones, a group of natural phytoestrogens, have only weak estrogenic activity and are not known to have side effects such as carcinogenesis and feminization, we evaluated the effects of genistein, daidzein and glycitein on the growth and DNA synthesis of aortic smooth muscle cells (SMC) from stroke-prone spontaneously hypertensive rats (SHRSP). SMC were cultured in dishes and proliferated on 10% dextran-coated charcoal/fetal bovine serum, and then treated with 0.1–30 µmol/L of genistein, daidzein or glycitein to investigate cell proliferation (cell number) and DNA synthesis (cell proliferation ELISA system), respectively. We also studied their effects on platelet-derived growth factor (PDGF)-BB (20 µg/L)–induced SMC proliferation. Soybean isoflavones inhibited proliferation and DNA synthesis of SMC from SHRSP in a concentration-dependent manner. Inhibition was significant at 3 µmol/L of genistein and 10 µmol/L of both daidzein and glycitein. For significant inhibition of PDGF-BB–induced SMC proliferation, concentrations as low as 0.1 µmol/L of each isoflavone were effective. These isoflavones, with their inhibitory effects on natural and PDGF-BB–induced SMC proliferation, may be useful in attenuatating such proliferation, a basic mechanism involved in atherosclerotic vascular change, thereby preventing atherosclerotic cardiovascular diseases.

KEY WORDS: • isoflavone • genistein • daidzein • glycitein • smooth muscle cells • rats

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