Mechanism of free Zn(2+) enhancing inhibitory effects of EGCG on the growth of PC-3 cells: interactions with mitochondria

Biol Trace Elem Res. 2009 Dec;131(3):298-310. doi: 10.1007/s12011-009-8362-5. Epub 2009 Mar 27.

Abstract

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. Zn(2+) 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 Zn(2+) was studied. These studies revealed that EGCG, Zn(2+), or EGCG + Zn(2+) affected the morphology of PC-3 cells and induced apoptosis in PC-3 cells. It was observed that effects of treatment with EGCG, Zn(2+), or EGCG + Zn(2+)on mitochondria showed EGCG + Zn(2+) > Zn(2+) > 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 + Zn(2+) > Zn(2+). In summary, these findings suggest that EGCG, Zn(2+), and EGCG + Zn(2+) induce necrosis or apoptosis of PC-3 cells through mitochondria-mediated apoptotic pathway and free Zn(2+)-enhanced effects of EGCG on PC-3 cells due to its interactions with mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • Apoptosis / drug effects
  • Caspase 9 / metabolism
  • Catechin / administration & dosage
  • Catechin / analogs & derivatives*
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Cytochromes c / metabolism
  • Drug Synergism
  • Humans
  • Male
  • Membrane Fluidity / drug effects
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Zinc / administration & dosage*

Substances

  • Adenosine Triphosphate
  • Catechin
  • Cytochromes c
  • epigallocatechin gallate
  • CASP9 protein, human
  • Caspase 9
  • Zinc