Role of Ku70 and Bax in epigallocatechin-3-gallate-induced apoptosis of A549 cells in vivo

Abstract

EGCG (epigallocatechin-3-gallate), the major catechin found in green tea, has been demonstrated to inhibit proliferation and induce apoptosis in a number of types of tumors. Recent studies reveal that EGCG has various anticancer effects. This study investigated a further possible molecular mechanism of the anticancer effects of EGCG in murine lung cancer xenografts. In the study, A549 human lung cancer cells were injected into nude mice. Tumor volume was used to measure cancer cell growth. The weight of the animals was used to assess the toxicity of the drugs. The expression of protein and mRNA was assayed by western blot analysis and RT-PCR, respectively. The interaction between Bax and Ku70 was determined by immunoprecipitation. Our results suggest that EGCG induced A549 lung cancer cell apoptosis in vivo, and had less toxic effects compared to classical anticancer drugs. EGCG may inhibit the surrogate markers of proliferation and apoptosis (caspase 3) in A549 tumor xenografts in vivo. In addition, EGCG downregulated the expression of Bcl-xl and upregulated the expression of Bax mRNA and protein. Further experiments indicated that EGCG downregulated the protein expression of Ku70 and interrupted the binding of Ku70 and Bax. This is the first study demonstrating that the induction of apoptosis by EGCG may be caused by the downregulation of Ku70 and that EGCG disrupts the interaction between Ku70 and Bax in lung cancer.