Inhibitory effect of caffeic acid phenethyl ester on angiogenesis, tumor invasion, and metastasis.
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.
Liao
Hui-Fen
HF
Department of Medical Research and Radiation Oncology, Mackay Memorial Hospital, Taipei 104, Taiwan.
Chen
Yu-Ywan
YY
Liu
Jun-Jen
JJ
Hsu
Ming-Ling
ML
Shieh
Hui-Ju
HJ
Liao
Hung-Jen
HJ
Shieh
Chwen-Jen
CJ
Shiao
Ming-Shi
MS
Chen
Yu-Jen
YJ
D000230:Adenocarcinoma; D000818:Animals; D002109:Caffeic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms; D042783:Endothelial Cells / Q000187:drug effects; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D010626:Phenylethyl Alcohol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D014471:Umbilical Veins; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
D002109:Caffeic Acids; D042461:Vascular Endothelial Growth Factor A; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol