Caffeic Acid Phenethyl Ester Suppresses the Proliferation of
Human Prostate Cancer Cells through Inhibition of p70S6K and Akt Signaling
Networks
Cancer Prev Res (Phila), 2012 May;5(5):788-97
Caffeic acid phenethyl ester (CAPE) is a bioactive component
derived from honeybee hive propolis. CAPE has been shown to have antimitogenic,
anticarcinogenic, and other beneficial medicinal properties. Many of its
effects have been shown to be mediated through its inhibition of NF-κB
signaling pathways.
We took a systematic approach to uncover the effects of CAPE
from hours to days on the signaling networks in human prostate cancer cells. We
observed that CAPE dosage dependently suppressed the proliferation of LNCaP,
DU-145, and PC-3 human prostate cancer cells. Administration of CAPE by gavage
significantly inhibited the tumor growth of LNCaP xenografts in nude mice.
Using LNCaP cells as
a model system, we examined the effect of CAPE on gene expression, protein
signaling, and transcriptional regulatory networks using micro-Western arrays
and PCR arrays. We built a model of the impact of CAPE on cell signaling which
suggested that it acted through inhibition of Akt-related protein signaling
networks. Overexpression of Akt1 or c-Myc, a downstream target of Akt
signaling, significantly blocked the antiproliferative effects of CAPE.
In summary, our results suggest that CAPE administration may
be useful as an adjuvant therapy for prostate and potentially other types of
cancers that are driven by the p70S6K and Akt signaling networks.
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