Abstract Title:

Pro-oxidative activities and dose-response relationship of (-)-epigallocatechin-3-gallate in the inhibition of lung cancer cell growth: a comparative study in vivo and in vitro.

Abstract Source:

Carcinogenesis. 2010 Feb 16. Epub 2010 Feb 16. PMID: 20159951

Abstract Author(s):

Guang-Xun Li, Yu-Kuo Chen, Zhe Hou, Hang Xiao, Huanyu Jin, Gary Lu, Mao-Jung Lee, Ba Liu, Fei Guan, Zhihong Yang, Albert Yu, Chung S Yang

Article Affiliation:

Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854.

Abstract:

(-)-Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, has been shown to inhibit tumorigenesis and cancer cell growth in animal models. Nevertheless, the dose-response relationship of the inhibitory activity in vivo has not been systematically characterized. The present studies were conducted to address these issues, as well as the involvement of reactive oxygen species (ROS), in the inhibitory action of EGCG in vivo and in vitro. We characterized the inhibitory actions of EGCG against human lung cancer H1299 cells in culture and in xenograft tumors. The growth of tumors was dose-dependently inhibited by EGCG at doses of 0.1%, 0.3% and 0.5% in the diet. Tumor cell apoptosis and oxidative DNA damage, assessed by the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and phosphorylated histone 2A variant X (gamma-H2AX), were dose-dependently increased by EGCG treatment. However, the levels of 8-OHdG and gamma-H2AX were not changed by the EGCG treatment in host organs. In culture, the growth of viable H1299 cells was dose-dependently reduced by EGCG; the estimated IC(50) (20 muM) was much higher than the IC(50) (0.15 muM) observed in vivo. The action of EGCG was mostly abolished by the presence of superoxide dismutase (SOD) and catalase, which decompose the ROS formed in the culture medium. Treatment with EGCG also caused the generation of intracellular ROS and mitochondrial ROS. Although EGCG is generally considered to be an antioxidant, the present study demonstrates the pro-oxidative activities of EGCG in vivo and in vitro in the described experimental system.

Study Type : In Vitro Study

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