Dataset Information

Copper chelation selectively kills colon cancer cells through redox cycling and generation of reactive oxygen species.

ABSTRACT:

Background

Metals including iron, copper and zinc are essential for physiological processes yet can be toxic at high concentrations. However the role of these metals in the progression of cancer is not well defined. Here we study the anti-tumor activity of the metal chelator, TPEN, and define its mechanism of action.

Methods

Multiple approaches were employed, including cell viability, cell cycle analysis, multiple measurements of apoptosis, and mitochondrial function. In addition we measured cellular metal contents and employed EPR to record redox cycling of TPEN-metal complexes. Mouse xenografts were also performed to test the efficacy of TPEN in vivo.

Results

We show that metal chelation using TPEN (5?M) selectively induces cell death in HCT116 colon cancer cells without affecting the viability of non-cancerous colon or intestinal cells. Cell death was associated with increased levels of reactive oxygen species (ROS) and was inhibited by antioxidants and by prior chelation of copper. Interestingly, HCT116 cells accumulate copper to 7-folds higher levels than normal colon cells, and the TPEN-copper complex engages in redox cycling to generate hydroxyl radicals. Consistently, TPEN exhibits robust anti-tumor activity in vivo in colon cancer mouse xenografts.

Conclusion

Our data show that TPEN induces cell death by chelating copper to produce TPEN-copper complexes that engage in redox cycling to selectively eliminate colon cancer cells.

SUBMITTER: Fatfat M

PROVIDER: S-EPMC4223620 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Publications

Copper chelation selectively kills colon cancer cells through redox cycling and generation of reactive oxygen species.

Fatfat Maamoun M Merhi Raghida Abou RA Rahal Omar O Stoyanovsky Detcho A DA Zaki Angela A Haidar Hazar H Kagan Valerian E VE Gali-Muhtasib Hala H Machaca Khaled K

BMC cancer 20140721

<h4>Background</h4>Metals including iron, copper and zinc are essential for physiological processes yet can be toxic at high concentrations. However the role of these metals in the progression of cancer is not well defined. Here we study the anti-tumor activity of the metal chelator, TPEN, and define its mechanism of action.<h4>Methods</h4>Multiple approaches were employed, including cell viability, cell cycle analysis, multiple measurements of apoptosis, and mitochondrial function. In addition ...[more]

PMID: 25047035

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Dataset Information

Copper chelation selectively kills colon cancer cells through redox cycling and generation of reactive oxygen species.

Background

Methods

Results

Conclusion

Publications

Copper chelation selectively kills colon cancer cells through redox cycling and generation of reactive oxygen species.

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