Mechanism of Free Zn(2+) Enhancing Inhibitory Effects of EGCG on the Growth of PC-3 Cells: Interactions with Mitochondria
2009
Yang, Junguo | Yu, Haining | Sun, Shili | Zhang, Lancui | Das, Undurti N. | Ruan, Hui | He, Guoqing | Shen, Shengrong
Green tea and its major constituent epigallocatechin gallate (EGCG) are known for their chemopreventive effects including those against prostate cancer, which could be mediated by metal ions. Zn²⁺ is an essential trace element that is required for human health and plays an important role in the normal function of the prostate gland. In the present study, the effect of EGCG on cell membrane and mitochondria of PC-3 (prostate carcinoma) cells in the presence and absence of Zn²⁺ was studied. These studies revealed that EGCG, Zn²⁺, or EGCG + Zn²⁺ affected the morphology of PC-3 cells and induced apoptosis in PC-3 cells. It was observed that effects of treatment with EGCG, Zn²⁺, or EGCG + Zn²⁺on mitochondria showed EGCG + Zn²⁺ > Zn²⁺ > EGCG, including cytochrome C release from the intermembrane space into the cytosol, inhibited the synthesis of ATP, loss of mitochondrial membrane potential, and activation of caspase-9. However, the order of effect on depressing membrane fluidity of PC-3 cells was EGCG > EGCG + Zn²⁺ > Zn²⁺. In summary, these findings suggest that EGCG, Zn²⁺, and EGCG + Zn²⁺ induce necrosis or apoptosis of PC-3 cells through mitochondria-mediated apoptotic pathway and free Zn²⁺-enhanced effects of EGCG on PC-3 cells due to its interactions with mitochondria.
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