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Int J Mol Sci. 2015 May 12;16(5):10748-66. doi: 10.3390/ijms160510748.

Caffeic Acid phenethyl ester is a potential therapeutic agent for oral cancer.

Kuo YY1,2,3, Jim WT4,5,6, Su LC7, Chung CJ8, Lin CY9, Huo C10,11, Tseng JC12,13,14, Huang SH15,16, Lai CJ17, Chen BC18,19,20, Wang BJ21,22,23, Chan TM24,25, Lin HP26, Chang WS27, Chang CR28, Chuu CP29,30,31,32.

Author information

1
Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli 35053, Taiwan. 034279@nhri.org.tw.
2
Institute of Biotechnology, National Tsing Hua University, Hsinchu City 30013, Taiwan. 034279@nhri.org.tw.
3
College of Life Science, National Tsing Hua University, Hsinchu City 30013, Taiwan. 034279@nhri.org.tw.
4
Department of Pediatrics, Mackay Memorial Hospital, Taipei City 10449, Taiwan. waitim@ms1.mmh.org.tw.
5
Department of Medicine, Mackay Medical College, New Taipei City 25245, Taiwan. waitim@ms1.mmh.org.tw.
6
Department of Early Childhood Care and Education, Mackay Junior College of Medicine, Nursing, and Management, New Taipei City 25245, Taiwan. waitim@ms1.mmh.org.tw.
7
Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli 35053, Taiwan. liangcheng610@nhri.org.tw.
8
Department of Health Risk Management, China Medical University, Taichung City 40402, Taiwan. cjchung@mail.cmu.edu.tw.
9
Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli 35053, Taiwan. cylin071@gmail.com.
10
Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli 35053, Taiwan. s103080810@m103.nthu.edu.tw.
11
Department of Life Sciences, National Central University, Taoyuan City 32001, Taiwan. s103080810@m103.nthu.edu.tw.
12
Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli 35053, Taiwan. s100080826@m100.nthu.edu.tw.
13
College of Life Science, National Tsing Hua University, Hsinchu City 30013, Taiwan. s100080826@m100.nthu.edu.tw.
14
Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu City 30013, Taiwan. s100080826@m100.nthu.edu.tw.
15
Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli 35053, Taiwan. hshf7855@gmail.com.
16
Department of Life Sciences, National Central University, Taoyuan City 32001, Taiwan. hshf7855@gmail.com.
17
Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli 35053, Taiwan. krad0127@gmail.com.
18
Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli 35053, Taiwan. s102080545@m102.nthu.edu.tw.
19
College of Life Science, National Tsing Hua University, Hsinchu City 30013, Taiwan. s102080545@m102.nthu.edu.tw.
20
Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu City 30013, Taiwan. s102080545@m102.nthu.edu.tw.
21
Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli 35053, Taiwan. bijuanwang1004@gmail.com.
22
College of Life Science, National Tsing Hua University, Hsinchu City 30013, Taiwan. bijuanwang1004@gmail.com.
23
Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu City 30013, Taiwan. bijuanwang1004@gmail.com.
24
Department of Medical Education and Research, China Medical University Beigang Hospital, Yunlin County 65152, Taiwan. ziv.j@yahoo.com.tw.
25
Department of Medical Education and Research, Tainan Municipal An-Nan Hospital, China Medical University, Tainan City 70965, Taiwan. ziv.j@yahoo.com.tw.
26
National Institute of Cancer Research, National Health Research Institutes, Miaoli 35053, Taiwan. diablofish@nhri.org.tw.
27
National Institute of Cancer Research, National Health Research Institutes, Miaoli 35053, Taiwan. wayne@nhri.org.tw.
28
Institute of Biotechnology, National Tsing Hua University, Hsinchu City 30013, Taiwan. crchang@life.nthu.edu.tw.
29
Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli 35053, Taiwan. cpchuu@nhri.org.tw.
30
Graduate Institute of Basic Medical Science and PhD Program for Aging, China Medical University, Taichung City 40402, Taiwan. cpchuu@nhri.org.tw.
31
Biotechnology Center, National Chung Hsing University, Taichung City 40227, Taiwan. cpchuu@nhri.org.tw.
32
PhD Program in Environmental and Occupational Medicine, Kaohsiung Medical University, Kaohsiung City 80708, Taiwan. cpchuu@nhri.org.tw.

Abstract

Head and neck cancers, which affect 650,000 people and cause 350,000 deaths per year, is the sixth leading cancer by cancer incidence and eighth by cancer-related death worldwide. Oral cancer is the most common type of head and neck cancer. More than 90% of oral cancers are oral and oropharyngeal squamous cell carcinoma (OSCC). The overall five-year survival rate of OSCC patients is approximately 63%, which is due to the low response rate to current therapeutic drugs. In this review we discuss the possibility of using caffeic acid phenethyl ester (CAPE) as an alternative treatment for oral cancer. CAPE is a strong antioxidant extracted from honeybee hive propolis. Recent studies indicate that CAPE treatment can effectively suppress the proliferation, survival, and metastasis of oral cancer cells. CAPE treatment inhibits Akt signaling, cell cycle regulatory proteins, NF-κB function, as well as activity of matrix metalloproteinase (MMPs), epidermal growth factor receptor (EGFR), and Cyclooxygenase-2 (COX-2). Therefore, CAPE treatment induces cell cycle arrest and apoptosis in oral cancer cells. According to the evidence that aberrations in the EGFR/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling, NF-κB function, COX-2 activity, and MMPs activity are frequently found in oral cancers, and that the phosphorylation of Akt, EGFR, and COX-2 correlates to oral cancer patient survival and clinical progression, we believe that CAPE treatment will be useful for treatment of advanced oral cancer patients.

KEYWORDS:

Akt; MMP; NF-κB; apoptosis; caffeic acid phenethyl ester; cell cycle arrest; cell proliferation; metastasis; oral cancer

PMID:
25984601
PMCID:
PMC4463674
DOI:
10.3390/ijms160510748
[Indexed for MEDLINE]
Free PMC Article

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