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Tumor Biology

, Volume 36, Issue 11, pp 8861–8867 | Cite as

Targeting increased copper levels in diethylnitrosamine induced hepatocellular carcinoma cells in rats by epigallocatechin-3-gallate

  • Mohd Farhan
  • Asim Rizvi
  • Imrana Naseem
  • S. M. Hadi
  • Aamir Ahmad
Research Article

Abstract

We have earlier elucidated a pathway for the anticancer action of plant polyphenolic compounds against malignant cells involving mobilisation of endogenous copper ions and the consequent prooxidant action. To further confirm our hypothesis in vivo, we induced hepatocellular carcinoma (HCC) in rats by diethylnitrosamine (DEN). We show that in such carcinoma cells, there is a progressive elevation in copper levels at various intervals after DEN administration. Concurrently with increasing copper levels, epigallocatechin-3-gallate (EGCG; a potent anticancer plant polyphenol found in green tea) mediated DNA breakage in malignant cells is also increased. The cell membrane permeable copper chelator neocuproine inhibited the EGCG-mediated cellular DNA degradation, whereas the membrane impermeable chelator bathocuproine was ineffective. Iron and zinc specific chelators desferoxamine mesylate and histidine, respectively, were also ineffective in inhibiting EGCG mediated DNA breakage. Through the use of specific scavengers, the mechanism of DNA breakage was determined to be mediated by reactive oxygen species. In summary, we provide an in vivo evidence of accumulating copper in hepatocellular carcinoma that is targeted by EGCG, leading to its anticancer role in a prooxidant manner. Our findings confirm a novel mechanism of anticancer activity of EGCG in particular and plant derived nutraceuticals in general.

Keywords

Copper Diethylnitrosamine EGCG Hepatocellular carcinoma Liver 

Notes

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Mohd Farhan
    • 1
  • Asim Rizvi
    • 1
    • 2
  • Imrana Naseem
    • 1
  • S. M. Hadi
    • 1
  • Aamir Ahmad
    • 3
  1. 1.Department of Biochemistry, Faculty of Life SciencesAMUAligarhIndia
  2. 2.Section of Radiobiology, Department of Radiology, The Biomedical Research TowerThe Ohio State UniversityColumbusUSA
  3. 3.Karmanos Cancer InstituteWayne State UniversityDetroitUSA

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