Caffeic Acid Phenethyl Ester Is a Potential Therapeutic Agent for Oral Cancer

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.

Mechanisms involved in the cytotoxic action of Brazilian propolis and caffeic acid against HEp-2 cells and modulation of P-glycoprotein activity

“…Several researches have shown the anticarcinogenic and proapoptotic effects of CAPE, but little is known regarding Caf effects. CAPE and Caf are different molecules with different physical, chemical and functional properties.…”

“…[17] Our results are in agreement with previous investigation showing that Brazilian green propolis inhibited different cancer cells by inducing apoptosis. [18][19][20] Several researches have shown the anticarcinogenic and proapoptotic effects of CAPE, [21][22][23] but little is known regarding Caf effects. CAPE and Caf are different molecules with different physical, chemical and functional properties.…”

NRSN2 promotes breast cancer metastasis by activating PI3K/AKT/mTOR and NF‑κB signaling pathways

“…All cells were cultured in Dulbecco's modified Eagle's medium (DMEM; Invitrogen; Thermo Fisher Scientific, Inc.) containing 10% fetal bovine serum (Invitrogen; Thermo Fisher Scientific, Inc.) and 1% penicillin/streptomycin (Invitrogen; Thermo Fisher Scientific, Inc.) and placed at 37˚C in a humidified incubator containing 5% CO 2 . Cells were treated with the NF-κB inhibitor caffeic acid phenethyl ester (CAPE; 70 mM; Apex Biotechnology Corp.), PI3K inhibitor (70 mM; Sigma-Aldrich; Merck KGaA) or PBS as control for 12 h at 37˚C for further experiments (15).…”

Synthesis, antifungal activity of caffeic acid derivative esters, and their synergism with fluconazole and nystatin against Candida spp.

“…Caffeic acid (3,4-dihydroxycinnamic acid) is an important phenolic compound commonly found in plants, foods, and propolis samples, particularly in the form of caffeic acid phenethyl ester (Paracatu et al, 2014;Rzepecka-Stojko et al, 2015). It is better known for its pharmacological properties, including antimicrobial, antioxidant, anti-inflammatory, and anticancer (Balachandran et al, 2012;Kuo et al, 2015). Nevertheless, modifications of the caffeic acid structure into esters or amides, for instance, may generate novel analog molecules with enhanced and desired biological activity (Touaibia et al, 2011), particularly as antimicrobials (Fu et al, 2010).…”