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Diallyl Sulfides (DAS) and Diallyl Disulfides (DADS) Exhibit a Suppressive Effect on the Proliferation and Migration of Vascular Smooth Muscle

  • Kim, Min-Ju (National Research Laboratory for Clinical Nutrigenetics/Nutrigenomics, Department of Food and Nutrition, Yonsei University) ;
  • Kwak, Jung-Hyun (National Research Laboratory for Clinical Nutrigenetics/Nutrigenomics, Department of Food and Nutrition, Yonsei University) ;
  • Baek, Seung-Han (Department of Biology, College of Natural Science, Yonsei University) ;
  • Yeo, Hyun-Yang (Research Institute National Cancer Center, Colorectal Cancer Branch) ;
  • Song, Ju-Hyun (National Research Laboratory for Clinical Nutrigenetics/Nutrigenomics, Department of Food and Nutrition, Yonsei University) ;
  • Cho, Bong-Jun (Interdisciplinary Course of Science for Aging Graduate School, Yonsei University) ;
  • Kim, Oh-Yoen (National Research Laboratory for Clinical Nutrigenetics/Nutrigenomics, Department of Food and Nutrition, Yonsei University)
  • 투고 : 2010.05.14
  • 심사 : 2010.06.15
  • 발행 : 2010.06.30

초록

Previous studies report that organo-sulfur compounds derived from garlic inhibited smooth muscle cell (SMC) proliferation and induced apoptosis of cancer cells. Recently, lipid-soluble compounds such as diallyl sulfides (DAS) and diallyl disulfides (DADS) have been reported to more effectively suppress tumor cell proliferation. However, there were few studies on the suppressive effects of lipid-soluble garlic sulfur compounds on the proliferation and migration of vascular smooth muscle cells (VSMC). Therefore, this study investigated the effect of DAS and DADS on VSMC proliferation/migration induced by oleic acid (OA), a principal fatty acid in circulating triglyceride of blood stream. Assays performed include a tetrazole (MTT) assay, a wound healing assay and a Western blots. VSMC proliferations were enhanced by OA in a dose-dependent manner at concentrations of $10{\sim}50\;{\mu}M$ and inhibited by DAS and DADS compared to non-treated control. OA-induced proliferations were also attenuated by DAS and DADS. OA-induced cell migrations were 2.5 times higher than non-treated control, and they were significantly attenuated by DAS (32% at $150\;{\mu}M$ and 50% at $200\;{\mu}M$) and DADS (40% at $150\;{\mu}M$ and 46% at $200\;{\mu}M$). OA-induced cell migration was also attenuated by PD98059 (ERK inhibitor), SB203580 (P38 inhibitor) and particularly by LY204002 (PI3K inhibitor) and SP600125 (JNK2 inhibitor). Additionally, Western blot assays showed that OA-induced JNK1/2-phosphorylation was down-regulated after treatment with DAS and DADS. In conclusion, the findings of our study support the idea that DAS and DADS may have a suppressive effect on the proliferation and migration of OA-induced VSMC and that this effect may be partly associated with PI3K and JNK2 pathways.

키워드

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