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- Title
Epigallocatechin Gallate Dose-Dependently Induces Apoptosis or Necrosis in Human MCF-7 Cells.
- Authors
HSUUW, YAN‐DER; CHAN, WEN‐HSIUNG
- Abstract
The catechins, a family of polyphenols found in tea, can evoke various responses, including cell death. However, the precise molecular mechanisms of these effects are unknown. Here, we demonstrate that treatment of human MCF-7 cells with 50 μM (-)-Epigallocatechin-3-gallate (EGCG), a catechin that is highly abundant in green tea, can induce apoptotic changes, including mitochondrial membrane potential changes and activation of c-Jun N-terminal kinase (JNK), caspase-9, and caspase-3. In contrast, higher concentrations of EGCG (100–400 μM) do not induce apoptosis, but rather trigger necrotic cell death in MCF-7 cells. Investigations of the possible mechanisms underlying these differences revealed that treatment with lower concentrations of EGCG (10–50 μM) directly increased intracellular oxidative stress, while higher concentrations (100–400 μM) did not. Immunoblotting revealed that treatment of MCF-7 cells with 10–50 μM EGCG caused increases in Bax protein levels and decreases in Bcl-2 protein levels, shifting the Bax–Bcl-2 ratio to favor apoptosis, while treatment with 100–400 μM EGCG had no such effect. Moreover, we observed a dose-dependent decrease in intracellular ATP levels in cells treated with high-dose EGCG. Blockade of reactive oxygen species (ROS) generation and ATP synthesis using antioxidants and ATP synthesis inhibitors revealed that ROS and ATP play important roles to switch cell death types with apoptosis or necrosis. Collectively, these results indicate for the first time that EGCG treatment has a dose-dependent effect on ROS generation and intracellular ATP levels in MCF-7 cells, leading to either apoptosis or necrosis, and that the apoptotic cascade involves JNK activation, Bax expression, mitochondrial membrane potential changes, and activation of caspase-9 and caspase-3.
- Subjects
CATECHIN; APOPTOSIS; CELL death; NECROSIS; BREAST cancer; CELL lines
- Publication
Annals of the New York Academy of Sciences, 2007, Vol 1095, Issue 1, p428
- ISSN
0077-8923
- Publication type
Article
- DOI
10.1196/annals.1397.046