Restoration of gap junctional intercellular communication by caffeic acid phenethyl ester (CAPE) in a ras-transformed rat liver epithelial cell line.
Caffeic acid phenethyl ester (CAPE), an active ingredient of honeybee propolis, has been identified as having anti-inflammatory, anti-viral and anti-cancer properties. Since the deficiency of gap junctional intercellular communication (GJIC) has been shown to be a characteristic of most cancer cells, this study was designed to test the hypothesis that the anti-carcinogenic activity of CAPE might be related to its ability to restore GJIC in tumorigenic GJIC-deficient cells (WB-ras2 cells). The results showed that CAPE restored GJIC, phosphorylation of connexin 43 (Cx43) and its normal localization on the plasma membrane in WB-ras2 cells after 3 days at 5 microg/ml concentration. Additionally, CAPE inhibited growth in soft agar and decreased the protein level of p21(ras). The results are consistent with the hypothesis that the anti-cancer mechanism of CAPE may be mediated by its ability to restore GJIC.
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Department of Pediatrics and Human Development, National Food Safety and Toxicology Center, Michigan State University, East Lansing 48824-1317, USA.
Wilson
M R
MR
Kang
K S
KS
Chang
C C
CC
Grunberger
D
D
Trosko
J E
JE
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology* / Q000633:toxicity; D002109:Caffeic Acids / Q000494:pharmacology* / Q000633:toxicity; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000235:genetics / Q000473:pathology; D018031:Connexin 43 / Q000096:biosynthesis / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017629:Gap Junctions / Q000187:drug effects* / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D011905:Genes, ras / Q000187:drug effects* / Q000502:physiology; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015689:Oncogene Protein p21(ras) / Q000096:biosynthesis / Q000235:genetics; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000633:toxicity; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016588:Anticarcinogenic Agents; D002109:Caffeic Acids; D018031:Connexin 43; D015689:Oncogene Protein p21(ras); C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol