Antiproliferative activity of paeoniflorin is through cell cycle arrest and the Fas/Fas ligand-mediated apoptotic pathway in human non-small cell lung cancer A549 cells

Clin Exp Pharmacol Physiol. 2008 Feb;35(2):141-7. doi: 10.1111/j.1440-1681.2007.04795.x. Epub 2007 Oct 17.

Abstract

1. Paeoniflorin (PF), isolated from the paeony root, is reported to have immunoregulatory, neuromuscular blocking, anticonvulsant, antihyperglycaemic and antihypotensive effects. 2. The present study investigated the antiproliferative activity of PF. The results showed that PF inhibited the proliferation of A549 by blocking cell cycle progression in the G(0)/G(1) phase and inducing apoptosis. 3. An ELISA showed that G(0)/G(1) phase arrest may be due to p53-independent induction of p21/wild-type p53-activated fragment 1 (WAF1). Increased protein expression of Fas/apoptosis-1 (APO-1) and its two ligands, membrane-bound Fas ligand and soluble Fas ligand, may be responsible for the PF-induced apoptosis. 4. This is the first study to show that the induction of p21/WAF1 and the activity of the Fas/Fas ligand apoptotic system may participate in the antiproliferative activity of PF in A549 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Benzoates / pharmacology*
  • Bridged-Ring Compounds / pharmacology*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Cycle / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Dose-Response Relationship, Drug
  • Fas Ligand Protein / metabolism*
  • Glucosides / pharmacology*
  • Humans
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Monoterpenes
  • Signal Transduction / drug effects
  • Time Factors
  • Tumor Suppressor Protein p53 / metabolism
  • fas Receptor / metabolism*

Substances

  • Antineoplastic Agents, Phytogenic
  • Benzoates
  • Bridged-Ring Compounds
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Fas Ligand Protein
  • Glucosides
  • Monoterpenes
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • fas Receptor
  • peoniflorin