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Antiproliferative effects of 6-anilino-5-chloro-1H-benzo[d]imidazole-4,7-dione in vascular smooth muscle cells

Title
Antiproliferative effects of 6-anilino-5-chloro-1H-benzo[d]imidazole-4,7-dione in vascular smooth muscle cells
Authors
Hong S.-Y.Kwak K.-W.Ryu C.-K.Kang S.-J.Chung K.-H.
Ewha Authors
유충규
SCOPUS Author ID
유충규scopus
Issue Date
2008
Journal Title
Bioorganic and Medicinal Chemistry
ISSN
0968-0896JCR Link
Citation
vol. 16, no. 2, pp. 644 - 649
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
It has been known that benzimidazol-4,7-diones have antiproliferative activity against various cancer cell lines. Recently, we have also reported that these compounds strongly inhibited the proliferation of vascular smooth muscle cell (SMC) and human umbilical vein endothelial cells (HUVECs). Although benzimidazol-4,7-diones have important biological activities, the molecular mechanism of the compounds in these cells remains to be elucidated. In order to investigate the anti-proliferation mechanism of the compounds in smooth muscle cell, we selected 6-anilino-6-chloro-5-chloro-1H-benzo{d}midazole-4,7-dione (BUD-0203) among 12 benzimidazol-4,7-dione derivatives and examined its antiproliferative effects. Phosphorylation of the extracellular-signal regulated kinase (ERK) reached a maximal level at 1 h after treatment with BUD-0203 and was sustained during the examined period. We also observed that phosphorylation of p38 reached a maximal level at 4 h and decreased to control levels after 8 h. These results showed that BUD-0203 sustainedly activated MAP kinase pathways in SMC. However, this compound did not induce cell cycle arrest in G1 or G2 phase in these cells. We also demonstrated that BUD-0203 not only induced apoptosis of SMC, but it also strongly inhibited SMC migration induced by platelet-derived growth factor (PDGF) or serum.Taken together, our experiments indicate that benzimidazol-4,7-diones induce apoptosis of smooth muscle cell via simultaneously prolonged activation of MAP kinase pathways including ERK, p38, and JNK/SAPK, similar with the apoptosis mechanism reported previously. © 2007 Elsevier Ltd. All rights reserved.
DOI
10.1016/j.bmc.2007.10.069
Appears in Collections:
약학대학 > 약학과 > Journal papers
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