The Synergistic Inhibition of Human Lung Cancer Cells by the Tea Polyphenol (-)-Epigallocatechin-3-gallate and Clinically Prescribed Inhibitors of Catechol-O-Methyltransferase
Open Access
- Author:
- Seitz, Adam E
- Area of Honors:
- Food Science
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Joshua D Lambert, Thesis Supervisor
Joshua D Lambert, Thesis Supervisor
Donald B Thompson, Thesis Honors Advisor - Keywords:
- Tolcapone
COMT
Catechol-O-methyltransferase
EGCG
(-)-Epigallocatechin-3-gallate
Entacapone
Green Tea
Cancer Chemoprevention
H1299 - Abstract:
- Tea, produced from the leaves of Camellia sinensis, was initially utilized for its medicinal properties nearly 5,000 years ago.1 Current worldwide consumption of tea as a beverage is second only to that of water, with approximately three billion kilograms being processed and consumed annually. Tea contains several polyphenolic compounds known as catechins. These catechins have been studied extensively for their cancer chemopreventive properties both in vitro and in vivo within animal and human systems. (-)-Epigallocatechin-3-gallate (EGCG) is the most abundant catechin and has been implicated as the most bioactive. Catechol-O-methyltransferase (COMT) is a phase II metabolizing enzyme that reduces the activity/toxicity of catechol structures through conjugation with methyl groups. EGCG is readily methylated by COMT in both rodents and humans. An increasing body of evidence suggests that methylation by COMT modulates the chemo-preventive activity of EGCG. The purpose of the present study was to determine if EGCG in combination with clinically used COMT inhibitors (entacapone and tolcapone) has synergistic anticancer effects in the H1299 human lung adenocarcinoma cell line. It was observed that the co-treatment of H1299 cells with EGCG and tolcapone or entacapone resulted in a greater than additive, and in some instances synergistic growth inhibitory effect. The mechanism by which this effect was derived cannot be fully elucidated by the current study, though it is expected that tolcapone and entacapone can enhance the chemopreventive activity of EGCG by inhibiting its methylation via COMT. Additionally, both tolcapone and entacapone exhibited significant cancer chemopreventive properties when used singly, and these effects additionally contribute to the activity of the combination. The results of this study support the hypothesis that COMT status modulates the cancer chemopreventive activity of the tea catechin EGCG. Furthermore, such evidence provides a mechanism-based rationale for the potential development of cancer chemopreventive regimens using EGCG, or EGCG analogs, in conjunction with COMT inhibitors such as tolcapone or entacapone.