Inhibitory effect of caffeic acid phenethyl ester on angiogenesis, tumor invasion, and metastasis

J Agric Food Chem. 2003 Dec 31;51(27):7907-12. doi: 10.1021/jf034729d.

Abstract

Caffeic acid phenethyl ester (CAPE) derived from honeybee propolis has been used as a folk medicine and has several proven biological activities. The present study investigated the effect of CAPE on angiogenesis, tumor invasion, and metastasis. A cytotoxicity assay of CAPE in CT26 colon adenocarcinoma cells showed a dose-dependent decrease in cell viability but no significant influence on the growth of human umbilical vein epithelial cells (HUVEC). A low concentration of CAPE (1.5 microg/mL) inhibited 52.7% of capillary-like tube formation in HUVEC culture on Matrigel. CAPE (6 microg/mL)-treated CT26 cells showed not only inhibited cell invasion by 47.8% but also decreased expression of matrix metalloproteinase (MMP)-2 and -9. Vascular endothelial growth factor (VEGF) production from CT26 cells was also inhibited by treatment with CAPE (6 microg/mL). Intraperitoneal injection of CAPE (10 mg/kg/day) in BALB/c mice reduced the pulmonary metastatic capacity of CT26 cells accompanied with a decreased plasma VEGF level. CAPE treatment also prolonged the survival of mice implanted with CT26 cells. These results indicate that CAPE has potential as an antimetastatic agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma
  • Animals
  • Caffeic Acids / administration & dosage
  • Caffeic Acids / therapeutic use*
  • Cell Division / drug effects
  • Cell Survival / drug effects
  • Colonic Neoplasms
  • Endothelial Cells / drug effects
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Invasiveness / prevention & control*
  • Neoplasm Metastasis / prevention & control*
  • Neoplasm Transplantation
  • Neovascularization, Pathologic / prevention & control*
  • Phenylethyl Alcohol / administration & dosage
  • Phenylethyl Alcohol / analogs & derivatives*
  • Phenylethyl Alcohol / therapeutic use*
  • Umbilical Veins
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors

Substances

  • Caffeic Acids
  • Vascular Endothelial Growth Factor A
  • caffeic acid phenethyl ester
  • Phenylethyl Alcohol