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

Abstract

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.

Effects of Epigallocatechin-3-gallate (EGCG) on A549 Lung Cancer Tumor Growth and Angiogenesis

“…These results are consistent with previous studies. [18][19][20] in which EGCG showed antiproliferative effects on lung cancer tumor in vivo, but failed to induce tumor regression.…”

“…In addition, a limited number of papers have reported effects of EGCG on lung cancer tumor growth in vivo. [18][19][20] Only one paper has reported an effect of EGCG on A549 tumor growth in vivo. 20)…”

Epigallocatechin-3-gallate inhibits cell growth, induces apoptosis and causes S phase arrest in hepatocellular carcinoma by suppressing the AKT pathway

“…Epigallocatechin-3-gallate (EGCG) is a water-soluble catechin, which suppresses the multiplication of cancer cells and induces apoptosis (3)(4)(5). EGCG suppressed adhesion and invasion of hepatocarcinoma cells through antioxidant activity (6).…”

Epigallocatechin gallate induces embryonic toxicity in mouse blastocysts through apoptosis

“…Although several studies have revealed that apoptosis functions in normal embryonic development (Brill et al, 1999;Lotz et al, 2006;Weingaertner et al, 2006), induction of excessive apoptosis by mechanistically diverse teratogens in early embryos leads to developmental injury (Chan, 2006(Chan, , 2007(Chan, , 2011Detmar et al, 2006;Hsuuw et al, 2005;Huang et al, 2003;Shang & Wu, 2004). EGCG has been shown to induce apoptosis (Kawai et al, 2005;Li et al, 2013). Data from the present study showed that EGCG suppresses embryonic cell proliferation during the blastocyst stage predominantly by apoptosis induction in the ICM and trophectoderm (TE).…”