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

Ying Yu Kuo, Hui Ping Lin, Chieh Huo, Liang Cheng Su, Jonathan Yang, Ping Hsuan Hsiao, Hung Che Chiang, Chi Jung Chung, Horng Dar Wang, Jang Yang Chang, Ya Wen Chen, Chih Pin Chuu

Research output: Contribution to journalArticlepeer-review

59 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)8801-8817
Number of pages17
JournalInternational journal of molecular sciences
Issue number5
Publication statusPublished - May 2013
Externally publishedYes


  • 5-fluorouracil
  • Akt
  • Akt1
  • Akt2
  • Caffeic acid phenethyl ester
  • Cell cycle
  • Cell proliferation
  • Cyclin D1
  • FOXO1
  • FOXO3a
  • NF- κB
  • Oral cancer
  • P27
  • Phospho-Akt Ser473
  • Phospho-Akt Thr 308
  • Phospho-FOXO1 Thr24
  • Phospho-FoxO3a Thr32
  • Phospho-NF- κB Ser536
  • Phospho-Rb Ser807/811
  • Rb
  • Skp2
  • TW2.6

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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