title: Caffeic acid phenethyl ester suppresses proliferation and survival of TW2.6 human oral cancer cells via inhibition of Akt signaling.
abstract: Caffeic acid phenethyl ester (CAPE) is a bioactive component extracted from honeybee hive propolis. Our observations indicated that CAPE treatment suppressed cell proliferation and colony formation of TW2.6 human oral squamous cell carcinoma (OSCC) cells dose-dependently. CAPE treatment decreased G1 phase cell population, increased G2/M phase cell population, and induced apoptosis in TW2.6 cells. Treatment with CAPE decreased protein abundance of Akt, Akt1, Akt2, Akt3, phospho-Akt Ser473, phospho-Akt Thr 308, GSK3β, FOXO1, FOXO3a, phospho-FOXO1 Thr24, phospho-FoxO3a Thr32, NF-κB, phospho-NF-κB Ser536, Rb, phospho-Rb Ser807/811, Skp2, and cyclin D1, but increased cell cycle inhibitor p27Kip. Overexpression of Akt1 or Akt2 in TW2.6 cells rescued growth inhibition caused by CAPE treatment. Co-treating TW2.6 cells with CAPE and 5-fluorouracil, a commonly used chemotherapeutic drug for oral cancers, exhibited additive cell proliferation inhibition. Our study suggested that administration of CAPE is a potential adjuvant therapy for patients with OSCC oral cancer.
authors.affiliation: Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli 35053, Taiwan. cpchuu@nhri.org.tw.
authors.forename: Ying-Yu
authors.initials: YY
authors.lastname: Kuo
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Lin
authors.forename: Chieh
authors.initials: C
authors.lastname: Huo
authors.forename: Liang-Cheng
authors.initials: LC
authors.lastname: Su
authors.forename: Jonathan
authors.initials: J
authors.lastname: Yang
authors.forename: Ping-Hsuan
authors.initials: PH
authors.lastname: Hsiao
authors.forename: Hung-Che
authors.initials: HC
authors.lastname: Chiang
authors.forename: Chi-Jung
authors.initials: CJ
authors.lastname: Chung
authors.forename: Horng-Dar
authors.initials: HD
authors.lastname: Wang
authors.forename: Jang-Yang
authors.initials: JY
authors.lastname: Chang
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Chen
authors.forename: Chih-Pin
authors.initials: CP
authors.lastname: Chuu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002109:Caffeic Acids / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D008954:Models, Biological; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014410:Tumor Stem Cell Assay
chemical_list: D002109:Caffeic Acids; D016328:NF-kappa B; D051057:Proto-Oncogene Proteins c-akt; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol; D005472:Fluorouracil