Raphanus sativus and its isothiocyanates inhibit vascular smooth muscle cells proliferation and induce G(1) cell cycle arrest.
Mu (Raphanus sativus, Korean White Radish) crude extract (Mu-CE) has been studied for its anti-proliferative activity on mouse aortic smooth muscle cells. The abnormal growth of vascular smooth muscle cells (VSMC) is a prominent feature of vascular disease, including atherosclerosis, restenosis after angioplasty. We examined the mechanisms of the action of Mu-CE on VSMC proliferation. The viability of VSMC decreased to 35% at 24 h of treatment with Mu-CE. Treatment of Mu-CE showed potent inhibitory effects on the DNA synthesis of cultured VSMC. In addition, Mu-CE induced apoptosis using cell death ELISA assay. These inhibitory effects were associated with G1 cell cycle arrest. Treatment of Mu-CE, which induced a cell-cycle arrest in G1-phase, induced down-regulation of cyclins and CDKs and up-regulation of the CDK inhibitor p21 expression, whereas up-regulation of p27 by Mu-CE was not observed. Then, total isothiocyanates (ITC) including four different 4-(Methylthio)-3-butenyl isothiocyanate (MTBITC), allyl isothiocayanate (AITC), benzyl isothiocyanate (BITC), and phenethyl isothiocyanate (PEITC) was isolated from n-hexane extracts of Mu. When the VSMC were treated with ITC, the cell viability was significantly decreased. These findings indicate the efficacy of Mu-CE in inhibiting cell proliferation, G1- to S-phase cell-cycle progress on VSMC.
Department of Biochemistry and Molecular Biology, Dongguk University College of Oriental Medicine and National Research Laboratory for Glycobiology, Sukjang-Dong 707, Kyungju, Kyungbuk 780-714, South Korea.
Seok-Jong
SJ
Suh
Sung-Kwon
SK
Moon
Cheorl-Ho
CH
Kim
D000818:Animals; D001011:Aorta; D017209:Apoptosis; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D019927:Cyclin E / Q000037:antagonists & inhibitors / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects; D017879:Isothiocyanates / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology; D031224:Raphanus / Q000737:chemistry*
D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D017879:Isothiocyanates; D010936:Plant Extracts; D019938:Cyclin D1; D051358:Cyclin-Dependent Kinase 4