Cytoprotection of human endothelial cells from menadione cytotoxicity by caffeic acid phenethyl ester: The role of heme oxygenase-1

Xinyu Wang, Salomon Stavchansky, Baiteng Zhao, James A. Bynum, Sean M. Kerwin, Phillip D. Bowman

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Caffeic acid phenethyl ester (CAPE), derived from various plant sources, has been shown to ameliorate ischemia/reperfusion injury in vivo, and this has been attributed to its ability to reduce oxidative stress. Here we investigated the cytoprotection of CAPE against menadione-induced oxidative stress in human umbilical vein endothelial cells (HUVEC) to evaluate potential gene expression involvement. CAPE exhibited dose-dependent cytoprotection of HUVEC. A gene screen with microarrays was performed to identify the potential cytoprotective gene(s) induced by CAPE. Heme oxygenase-1 (HO-1) was highly upregulated by CAPE and this was confirmed with reverse transcriptase polymerase chain reaction (RT-PCR) and western blotting. Inhibition of HO-1 activity using the HO-1 inhibitor tin protoporphyrin IX (SnPPIX), resulted in loss of cytoprotection. Carbon monoxide, one of HO-1 catabolic products appeared to play a small role in CAPE protection. Caffeic acid, a potential metabolite of CAPE with similar free radical scavenging ability, however, didn't show any cytoprotective effect nor induce HO-1. These findings suggest an important role of HO-1 induction in CAPE cytoprotection against oxidant stress, which may not relate to CAPE structural antioxidant activity nor to its traditional enzymatic activity in decomposing heme but to a yet to be determined activity.

Original languageEnglish (US)
Pages (from-to)28-35
Number of pages8
JournalEuropean Journal of Pharmacology
Issue number1-3
StatePublished - Sep 4 2008
Externally publishedYes


  • Caffeic acid phenethyl ester
  • Cytoprotection
  • Gene expression analysis
  • Heme oxygenase-1
  • Human endothelial cell
  • Oxidative stress

ASJC Scopus subject areas

  • Pharmacology


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