Potent Inhibition of Platelet-Derived Growth Factor-Stimulated Rat Aortic Vascular Smooth Muscle Cell Cycle and Proliferation by (2E)-3-(4-hydroxy-3-methoxy pheny I )pheny I pro-2-en-1 -one, a Newly Synthesized Benzyl ideneacetophenone Derivative

摘要

One of the principal regulators of mitogene-sis in vascular smooth muscle cells (VSMCs) is platelet-derived growth factor-BB (PDGF-BB). An increase of PDGF-BB expression has been observed in atherosclerotic lesions. The aim of this study was to elucidate the effects and molecular mechanism of (2E)-3-(4-hydroxy-3-methoxyphenyl)phenylpro-2-en-l-one (KTJ2242), a newly synthesized benzylide-neacetophenone derivative, on PDGF-BB-stimulated rat aortic VSMCs. KTJ2242 induced accumulation of cells in the Gl phase of the cell cycle of VSMCs. We observed that KTJ2242 inhibited PDGF-BB-stimulated [~3H]-thymidine incorporation into the DNA of VSMCs, and the cell number was significantly reduced in a concentration-dependent manner.Also, we observed that KTJ2242 decreased PDGF-BB-stimulated extracellular-regulated kinase 1 and 2 (ERK1/2) and Akt phosphorylation. These results suggest the possibility that KTJ2242 may be a potential agent with which to control vascular disorders and its antiproliferative mechanism may be mediated through partial Akt and ERKl/2-dependent signaling pathways.