Caffeic acid phenethyl ester-induced PC-3 cell apoptosis is caspase-dependent and mediated through the loss of inhibitors of apoptosis proteins

BJU Int. 2004 Aug;94(3):402-6. doi: 10.1111/j.1464-410X.2004.04936.x.


Objective: To investigate the effects of a novel agent, caffeic acid phethyl ester (CAPE) on nuclear factor (NF)-kappaB activation and apoptosis in the androgen-independent PC3 prostate cancer cell line.

Materials and methods: PC-3 cells were assessed for NF-kappaB activation induced by paclitaxel and tumour necrosis factor-alpha (TNF-alpha), using a p65 enzyme-linked immunosorbent assay, with or without CAPE treatment. The corresponding apoptosis was assessed with propidium iodide DNA staining using flow cytometry. The pan-caspase inhibitor Z-VAD-FMK was used to investigate the mechanism of apoptosis. Alterations in the expression of inhibitor of apoptosis proteins (IAP), cIAP-1, cIAP-2 and XIAP, were detected using western blot analysis.

Results: CAPE prevented paclitaxel and TNFalpha-mediated NF-kappaB activation. Its ability to induce apoptosis in a dose-dependent manner was associated with the loss of cIAP-1, cIAP-2 and XIAP expression. Pretreatment with Z-VAD-FMK prevented CAPE-induced apoptosis and the loss of the IAPs.

Conclusions: CAPE is an effective inhibitor of NF-kappaB activation in PC-3 cells, but the mechanism of apoptosis, and the corresponding loss of IAP expression, is caspase-dependent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Blotting, Western
  • Caffeic Acids / pharmacology*
  • Caspase Inhibitors*
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Male
  • NF-kappa B / metabolism*
  • Paclitaxel / pharmacology
  • Phenylethyl Alcohol / analogs & derivatives*
  • Phenylethyl Alcohol / pharmacology*
  • Prostatic Neoplasms / pathology*
  • Tumor Necrosis Factor-alpha / pharmacology


  • Caffeic Acids
  • Caspase Inhibitors
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • caffeic acid phenethyl ester
  • Phenylethyl Alcohol
  • Paclitaxel