Cinnamon and its Components Suppress Vascular Smooth Muscle Cell Proliferation by Up-Regulating Cyclin-Dependent Kinase Inhibitors

Am J Chin Med. 2015;43(4):621-36. doi: 10.1142/S0192415X1550038X. Epub 2015 Jun 28.

Abstract

Cinnamomum cassia bark has been used in traditional herbal medicine to treat a variety of cardiovascular diseases. However, the antiproliferative effect of cinnamon extract on vascular smooth muscle cells (VSMCs) and the corresponding restenosis has not been explored. Hence, after examining the effect of cinnamon extract on VSMC proliferation, we investigated the possible involvement of signal transduction pathways associated with early signal and cell cycle analysis, including regulatory proteins. Besides, to identify the active components, we investigated the components of cinnamon extract on VSMC proliferation. Cinnamon extract inhibited platelet-derived growth factor (PDGF)-BB-induced VSMC proliferation and suppressed the PDGF-stimulated early signal transduction. In addition, cinnamon extract arrested the cell cycle and inhibited positive regulatory proteins. Correspondingly, the protein levels of p21 and p27 not only were increased in the presence of cinnamon extract, also the expression of proliferating cell nuclear antigen (PCNA) was inhibited by cinnamon extract. Besides, among the components of cinnamon extract, cinnamic acid (CA), eugenol (EG) and cinnamyl alcohol significantly inhibited the VSMC proliferation. Overall, the present study demonstrates that cinnamon extract inhibited the PDGF-BB-induced proliferation of VSMCs through a G0/G1 arrest, which down-regulated the expression of cell cycle positive regulatory proteins by up-regulating p21 and p27 expression.

Keywords: Antiproliferative Activity; Cell cycle; Cinnamomum cassia Bark; Cyclin-Dependent Kinase Inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle / drug effects
  • Cell Cycle / genetics
  • Cell Proliferation / drug effects*
  • Cell Proliferation / genetics*
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Cells, Cultured
  • Cinnamomum zeylanicum / chemistry*
  • Cyclin-Dependent Kinase Inhibitor Proteins / metabolism*
  • Depression, Chemical
  • Muscle Cells / cytology*
  • Muscle Cells / metabolism
  • Muscle, Smooth, Vascular / cytology*
  • Muscle, Smooth, Vascular / metabolism
  • Plant Extracts / pharmacology*
  • Rats
  • Up-Regulation / drug effects*

Substances

  • Cyclin-Dependent Kinase Inhibitor Proteins
  • Plant Extracts