AN N-terminal Smac peptide sensitizes human prostate carcinoma cells to methyl jasmonate-induced apoptosis

Cancer Lett. 2011 Mar 1;302(1):37-46. doi: 10.1016/j.canlet.2010.12.009. Epub 2011 Jan 14.

Abstract

Although the anti-cancer agent methyl jasmonate (MJ) has been shown to selectively target malignant cells while sparing normal ones, hormone-refractory prostate cancer cells are relatively resistant to MJ than other cancer cells. In the present study, we investigated the effect of cell permeable seven-residue peptide of Smac (SmacN7), an antagonist of the inhibitor of apoptosis proteins (IAPs), on MJ-induced apoptosis. SmacN7 significantly enhanced the growth inhibition effect of MJ in human prostate cancer cells, but not in proximal tubular epithelial cells. Moreover, SmacN7 sensitizes MJ-induced apoptosis through both caspase-9-dependent and -independent pathways. Thus, blockade of the over-expressed IAPs in cancer cells could yield a potential therapeutic benefit in jasmonates-based chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / pharmacology*
  • Amino Acid Sequence
  • Apoptosis / drug effects*
  • Blotting, Western
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cyclopentanes / pharmacology*
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Drug Synergism
  • Humans
  • Inhibitor of Apoptosis Proteins / antagonists & inhibitors
  • Inhibitor of Apoptosis Proteins / metabolism
  • Male
  • Oligopeptides / metabolism
  • Oligopeptides / pharmacology*
  • Oxylipins / pharmacology*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Signal Transduction / drug effects
  • X-Linked Inhibitor of Apoptosis Protein / metabolism

Substances

  • Acetates
  • Cyclopentanes
  • Inhibitor of Apoptosis Proteins
  • Oligopeptides
  • Oxylipins
  • SMAC peptide
  • X-Linked Inhibitor of Apoptosis Protein
  • XIAP protein, human
  • methyl jasmonate
  • Caspase 3
  • Caspase 9