title: Caffeic acid phenethyl ester suppresses the proliferation of human prostate cancer cells through inhibition of p70S6K and Akt signaling networks.
abstract: 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.
authors.affiliation: The Ben May Department for Cancer Research, The University of Chicago, IL 60637, USA.
authors.forename: Chih-Pin
authors.initials: CP
authors.lastname: Chuu
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Lin
authors.forename: Mark F
authors.initials: MF
authors.lastname: Ciaccio
authors.forename: John M
authors.initials: JM
authors.lastname: Kokontis
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Hause
authors.forename: Richard A
authors.initials: RA
authors.lastname: Hiipakka
authors.forename: Shutsung
authors.initials: S
authors.lastname: Liao
authors.forename: Richard Baker
authors.initials: RB
authors.lastname: Jones
mesh_terms: D000818:Animals; D002109:Caffeic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003603:Cytotoxins / Q000494:pharmacology / Q000627:therapeutic use; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D002109:Caffeic Acids; D003603:Cytotoxins; D051058:Oncogene Protein v-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol