Inhibitory Effect of Caffeic Acid Phenethyl Ester on Angiogenesis, Tumor Invasion, and Metastasis

Hui Fen Liao, Yu Ywan Chen, Jun Jen Liu, Ming Ling Hsu, Hui Ju Shieh, Hung Jen Liao, Chwen Jen Shieh, Ming Shi Shiao, Yu Jen Chen

Research output: Contribution to journalArticlepeer-review

173 Citations (Scopus)


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 μg/mL) inhibited 52.7% of capillary-like tube formation in HUVEC culture on Matrigel. CAPE (6 μg/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 μg/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.

Original languageEnglish
Pages (from-to)7907-7912
Number of pages6
JournalJournal of Agricultural and Food Chemistry
Issue number27
Publication statusPublished - Dec 31 2003
Externally publishedYes


  • Angiogenesis
  • CAPE (caffeic acid phenethyl ester)
  • Human umbilical vein endothelial cell
  • Matrix metalloproteinase
  • Metastasis
  • Tumor invasion
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Food Science
  • Chemistry (miscellaneous)


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