Green tea component, catechin, induces apoptosis of human malignant B cells via production of reactive oxygen species

Purpose: Green tea polyphenol, (-)-epigallocatechin-3-gallate, has been shown to inhibit cellular proliferation and induce Apoptosis of various Cancer cells. The aim of this study was to investigate the possibility of (-)-epigallocatechin-3-gallate as a novel therapeutic agent for the patients with B-cell malignancies including multiple myeloma.

Experimental design: We investigated the effects of (-)-epigallocatechin-3-gallate on the induction of Apoptosis in HS-sultan as well as myeloma cells in vitro and further examined the molecular mechanisms of (-)-epigallocatechin-3-gallate-induced Apoptosis.

Results: (-)-Epigallocatechin-3-gallate rapidly induced apoptotic cell death in various malignant B-cell lines in a dose- and time-dependent manner. (-)-Epigallocatechin-3-gallate-induced Apoptosis was in association with the loss of mitochondrial transmembrane potentials (Deltapsim); the release of cytochrome c, Smac/DIABLO, and AIF from mitochondria into the cytosol; and the activation of Caspase-3 and caspase-9. Elevation of intracellular Reactive Oxygen Species (ROS) production was also shown during (-)-epigallocatechin-3-gallate-induced Apoptosis of HS-sultan and RPMI8226 cells as well as fresh myeloma cells. Antioxidant, catalase, and Mn superoxide dismutase significantly reduced ROS production and (-)-epigallocatechin-3-gallate-induced Apoptosis, suggesting that ROS plays a key role in (-)-epigallocatechin-3-gallate-induced Apoptosis in B cells. Furthermore, a combination with arsenic trioxide (As2O3) and (-)-epigallocatechin-3-gallate significantly enhanced induction of Apoptosis compared with As2O3 alone via decreased intracellular reduced glutathione levels and increased production of ROS.

Conclusions: (-)-Epigallocatechin-3-gallate has potential as a novel therapeutic agent for patients with B-cell malignancies including multiple myeloma via induction of Apoptosis mediated by modification of the redox system. In addition, (-)-epigallocatechin-3-gallate enhanced As2O3-induced Apoptosis in human multiple myeloma cells.