Caffeic acid phenethyl ester suppresses proliferation and survival of TW2.6 human oral cancer cells via inhibition of Akt signaling

• Published in: International journal of molecular sciences 2013-04, Vol.14 (5), p.8801-8817
• Main Authors: Kuo, Ying-Yu, Lin, Hui-Ping, Huo, Chieh, Su, Liang-Cheng, Yang, Jonathan, Hsiao, Ping-Hsuan, Chiang, Hung-Che, Chung, Chi-Jung, Wang, Horng-Dar, Chang, Jang-Yang, Chen, Ya-Wen, Chuu, Chih-Pin
• Format: Article
• Language: English
• Subjects: 5-fluorouracil; Acids; Akt; Akt1; Akt2; Alcohol use; Apoptosis - drug effects; Bees; caffeic acid phenethyl ester; Caffeic Acids - pharmacology; Cell cycle; Cell Cycle - drug effects; Cell growth; Cell Line, Tumor; cell proliferation; Cell Proliferation - drug effects; Cell Survival - drug effects; cyclin D1; Drug dosages; Drug Synergism; Fluorouracil - pharmacology; FOXO1; FOXO3a; Head & neck cancer; Humans; Medical prognosis; Medical research; Models, Biological; Mouth Neoplasms - enzymology; Mouth Neoplasms - pathology; NF-kappa B - metabolism; NF-κB; Oral cancer; p27; Phenylethyl Alcohol - analogs & derivatives; Phenylethyl Alcohol - pharmacology; phospho-Akt Ser473; phospho-Akt Thr 308; phospho-FOXO1 Thr24; phospho-FoxO3a Thr32; phospho-NF-κB Ser536; phospho-Rb Ser807/811; Phosphorylation - drug effects; Prostate; Proto-Oncogene Proteins c-akt - metabolism; Research centers; Signal Transduction - drug effects; Skp2; Smoking; Tobacco; Tumor Stem Cell Assay; TW2.6
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms14058801

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.