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Investigations of the cytotoxicity of epigallocatechin-3-gallate against PC-3 cells in the presence of Cd2+ in vitro.

Zhang LC, Yu HN, Sun SL, Yang JG, He GQ, Ruan H, Shen SR

Hua Jia Chi Campus, Zhejiang University, Hangzhou 310029, PR China.

The epidemiological studies and recent data have provided convinced evidence that green tea and its major constituent epigallocatechin gallate (EGCG) might have the potential to lower the risk of cancers in humans. Metal ions, such as zinc and cadmium, which are necessary to our health, are important factors inducing many diseases including prostate cancer in the condition of absence or excess. EGCG can satisfactorily exhibit complex chemistry with metal ions because of multiple hydroxyl states, which in turn changes their bioactivities and metabolism pathways. This paper presents the results of an investigation of the cytotoxicity of EGCG against PC-3 prostate cancer cells in the presence and absence of Cd2+ in vitro. The results showed that both EGCG and Cd2+ suppressed viability and clonegenecity of PC-3 cells, and the suppression effect was enhanced when EGCG added with Cd2+. Although Cd2+ up-regulated the 67 kDa laminin receptor (67LR), which is a migration-associated protein, the cell migration ability was not significantly increased after each treatment. We also found that EGCG and Cd2+ directly interacted with mitochondrial, and the mixture of EGCG and Cd2+ (EGCG+Cd2+) significantly caused loss of the mitochondrial membrane potential, decrease of the ATP content and activation of caspase-9 compared with EGCG treated alone. Taken together, these findings suggest that Cd2+ enhanced the cytotoxicity of EGCG to PC-3 cells by up-regulating the 67LR and the mitochondria-mediated apoptosis pathway.

Published 18 April 2008 in Toxicol In Vitro, 22(4): 953-60.
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