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 μM) 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 G₀/G₁ phase, which was related to the down-regulation of cell cycle regulatory factors such as cyclin D₁/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.