Pseudolaric acid B induces apoptosis via activation of c-Jun N-terminal kinase and caspase-3 in HeLa cells

Exp Mol Med. 2004 Dec 31;36(6):551-6. doi: 10.1038/emm.2004.70.

Abstract

Pseudolaric acid B was isolated from Pseudolarix kaempferi Gordon (Pinaceae) and was evaluated for the anti-cancer effect in HeLa cells. We ob-served that pseudolaric acid B inhibited cell proliferation and induced apoptosis in a time- and dose-dependent manner. HeLa cells treated with pseudolaric acid B showed typical characteristics of apoptosis including the morphological changes and DNA fragmentation. JNK inhibitor, SP600125,markedly inhibited pseudolaric acid B-induced celldeath. In addition, Bcl-2 expression was down-regulated while Bax protein level was up-regulated.Caspase-3 inhibitor, z-DEVD-fmk, partially blocked pseudolaric acid B-induced cell death, and the expression of two classical caspase substrates,PARP and ICAD, were both decreased in a time-dependent manner, indicative of downstream cas-pase activation.

MeSH terms

  • Anthracenes / pharmacology
  • Apoptosis*
  • Caspase 3
  • Caspase Inhibitors
  • Caspases / metabolism*
  • Cell Proliferation / drug effects
  • Cysteine Proteinase Inhibitors / pharmacology
  • Diterpenes / pharmacology*
  • Down-Regulation
  • Enzyme Activation
  • HeLa Cells
  • Humans
  • JNK Mitogen-Activated Protein Kinases / drug effects
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Oligopeptides / pharmacology
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction / drug effects*
  • Up-Regulation
  • bcl-2-Associated X Protein
  • bcl-X Protein

Substances

  • Anthracenes
  • BAX protein, human
  • BCL2L1 protein, human
  • Caspase Inhibitors
  • Cysteine Proteinase Inhibitors
  • Diterpenes
  • Oligopeptides
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone
  • pyrazolanthrone
  • pseudolaric acid B
  • JNK Mitogen-Activated Protein Kinases
  • CASP3 protein, human
  • Caspase 3
  • Caspases