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 (5μM) selectively induces cell death in HCT116 colon cancer cells wi

SUBMITTER: Fatfat M 

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

REPOSITORIES: biostudies-literature