JY0691, a newly synthesized obovatol derivative, inhibits cell cycle progression of rat aortic smooth muscle cells through up-regulation of p21(cip1).
Obovatol is known to have various biological activities such as muscle relaxation, anti-gastric ulcer, anti-inflammatory, anti-allergic, and anti-bacterial activities. We examined the effects of JY0691, a newly synthesized obovatol derivative, on the viability and proliferation in rat aortic smooth muscle cells. We also determined the mechanism by which the compound induces cell cycle arrest of the cells. Treatment with JY0691 (0-3 microM) inhibited proliferation of the cells in a dose-dependent manner without any cytotoxic effect. JY0691 treatment did not decrease the levels of platelet-derived growth factor (PDGF) receptor and several protein kinases which had stimulated by exposing the cells to 25 ng/ml PDGF-BB. In contrast, the compound arrested the cell cycle progression in the G(0)/G(1) phase, which was related to the down-regulation of cell cycle regulatory factors such as cyclin D(1)/E, cyclin-dependent kinase (CDK)2/4, and proliferating cell nuclear antigen. Further, JY0691 induced cell cycle arrest in the G1 phase through up-regulation of p21(cip1), but not of p27(kip1), where p53-mediated signaling was in part involved. Our current findings suggest that JY0691 contains anti-proliferative potential on aortic smooth muscle cells.
Yu
Ji-Yeon
JY
Institute for Molecular Biology and Genetics, Chonbuk National University, Jeonju 561-756, Republic of Korea.
Lee
Jung-Jin
JJ
Jung
Jae-Kyung
JK
Kim
Tack-Joong
TJ
Yoo
Hwan-Soo
HS
Yun
Yeo-Pyo
YP
Lee
Jeong-Chae
JC
D000818:Animals; D001011:Aorta / Q000166:cytology*; D001713:Biphenyl Compounds / Q000737:chemistry* / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010647:Phenyl Ethers / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects*
C547829:3-(4-propylphenoxy)-4,5-dihydroxybenzoic acid methyl ester; D001713:Biphenyl Compounds; D050759:Cyclin-Dependent Kinase Inhibitor p21; D010647:Phenyl Ethers; C036795:obovatol