Caffeic Acid Phenethyl Ester Suppresses Proliferation and
Survival of TW2.6 Human Oral Cancer Cells via Inhibition of Akt Signaling
Int. J. Mol. Sci, 2013, 14(5), 8801-8817
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.
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