Selective death of cancer cells by preferential induction of reactive oxygen species in response to (-)-epigallocatechin-3-gallate

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Source: www.sciencedirect.com --- Sunday, April 01, 2012
Publication year: 2012 Source: Biochemical and Biophysical Research Communications Na Young Min, Jin-Hong Kim, Jee-Hye Choi, Wen Liang, Young-Jong Ko, Sangmyung Rhee, Hyoweon Bang, Seung Wook Ham, Ae Ja Park, Kwang-Ho Lee (-)-Epigallocatechin-3-gallate (EGCG) induces apoptosis in Cancer cells without adversely affecting normal cells. Understanding the Cancer-specific cytotoxic activity of EGCG is very important in defining the mechanism of tumorigenesis and identifying superb chemotherapeutic agents against Cancer. We comparatively assayed human telomerase reverse transcriptase ( hTERT) -mediated apoptosis by EGCG-induced reactive oxygen species (ROS) in normal cells and Cancer cells. EGCG showed differential levels of ROS induction between the cell types; ROS, especially hydrogen peroxide, was highly induced in Cancer cells, while it was not in normal cells. In addition, the higher level of ROS down-regulated hTERT via binding of CCCTC binding factor (CTCF) to the core promoter region of hTERT , which repressed hTERT expression. CTCF binding was epigenetically controlled by the demethylation of the previously hypermethylated site for CTCF, which was induced by down-regulation of DNA methyltransferase 1 ( DNMT1 ). In contrast, hTERT down-regulation was not observed in normal cells. These results suggest that preferential death of Cancer cells by EGCG could be caused by the Cancer-specific induction of ROS and epigenetic modulatio ...

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