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Int. J. Mol. Sci. 2013, 14(5), 8801-8817; doi:10.3390/ijms14058801
Article

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

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Received: 1 March 2013; in revised form: 2 April 2013 / Accepted: 15 April 2013 / Published: 24 April 2013
(This article belongs to the Section Molecular Pathology)
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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.
Keywords: 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 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
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Kuo, Y.-Y.; Lin, H.-P.; Huo, C.; Su, L.-C.; Yang, J.; Hsiao, P.-H.; Chiang, H.-C.; Chung, C.-J.; Wang, H.-D.; Chang, J.-Y.; Chen, Y.-W.; Chuu, C.-P. 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, 8801-8817.

AMA Style

Kuo Y-Y, Lin H-P, Huo C, Su L-C, Yang J, Hsiao P-H, Chiang H-C, Chung C-J, Wang H-D, Chang J-Y, Chen Y-W, Chuu C-P. 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. 2013; 14(5):8801-8817.

Chicago/Turabian Style

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. 2013. "Caffeic Acid Phenethyl Ester Suppresses Proliferation and Survival of TW2.6 Human Oral Cancer Cells via Inhibition of Akt Signaling." Int. J. Mol. Sci. 14, no. 5: 8801-8817.



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