Caffeic Acid Phenethyl Ester Suppresses Proliferation and Survival of TW2.6 Human Oral Cancer Cells via Inhibition of Akt Signaling

International Journal of Molecular Sciences

Ying-Yu Kuo³  Hui-Ping Lin³  Chieh Huo³  Liang-Cheng Su³  Jonathan Yang³  Ping-Hsuan Hsiao³  Hung-Che Chiang¹  Chi-Jung Chung⁶  Horng-Dar Wang²  Jang-Yang Chang⁵  Ya-Wen Chen⁴ 

[1] Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Miaoli 35053, Taiwan; E-Mail:;Institute of Biotechnology, National Tsing Hua University, Hsinchu City 30013, Taiwan; E-Mail:;Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli 35053, Taiwan; E-Mails:;National Institute of Cancer Research, National Health Research Institutes, Miaoli 35053, Taiwan; E-Mail:;Translational Center for Glandular Malignancies, National Health Research Institutes, Miaoli 35053, Taiwan; E-Mail:;Department of Health Risk Management, China Medical University, Taichung City 40402, Taiwan; E-Mail:

关键词: oral cancer;    caffeic acid phenethyl ester;    TW2.6;    cell proliferation;    cell cycle;    Akt;    Akt1;    Akt2;    phospho-Akt Ser473;    phospho-Akt Thr 308;    FOXO1;    FOXO3a;    phospho-FOXO1 Thr24;    phospho-FoxO3a Thr32;    NF-κB;    phospho-NF-κB Ser536;    Rb;    phospho-Rb Ser807/811;    Skp2;    cyclin D1;    p27;    5-fluorouracil;   

DOI  :  10.3390/ijms14058801

来源: mdpi

【 摘 要 】

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 p27^Kip. 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.

【 授权许可】

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