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

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

doi:10.3390/ijms14058801

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.

Highlights

Head and neck cancers rank the 6th most common cancers worldwide, affecting 650,000 people and causing 350,000 deaths per year [1,2]
Hoechst dye-based proliferation assay indicated that Caffeic acid phenethyl ester (CAPE) treatment suppressed the proliferation of TW2.6 human oral squamous cell carcinoma (OSCC) cancer cells (Figure 1A)
The IC50 detected by MTT assay was very similar to the IC50 detected by Hoechst dye-based proliferation assay, suggesting that inhibition of cell proliferation was responsible for the reduction of viable cells caused by CAPE

Summary

Introduction

Head and neck cancers rank the 6th most common cancers worldwide, affecting 650,000 people and causing 350,000 deaths per year [1,2]. Oral cancer is the most frequent cancer of head and neck cancers. There were approximately 400,000 new cases and 200,000 deaths of OSCC worldwide in 2008 (http://www-dep.iarc.fr/) [3]. The overall 5-year survival rate of OSCC patients is approximately 60% [4]. The poor prognosis of OSCC is due to the low response rate to current therapeutic drugs [2]. Environmental carcinogens, such as betel quid chewing, tobacco smoking, and alcohol drinking, have been identified as major risk factors for head and neck cancers [5]. The incidence of oral cancer is highest in Southeast Asia and central

Methods

Results

Conclusion