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The Scientific World Journal
Volume 2014 (2014), Article ID 540463, 12 pages
http://dx.doi.org/10.1155/2014/540463
Research Article

A Schiff Base-Derived Copper (II) Complex Is a Potent Inducer of Apoptosis in Colon Cancer Cells by Activating the Intrinsic Pathway

1Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
2Faculty of Science, Institute of Biological Science, University of Malaya, 50603 Kuala Lumpur, Malaysia
3Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
4Department of Chemistry, University of Malaya, University of Malaya, 50603 Kuala Lumpur, Malaysia

Received 15 November 2013; Accepted 16 January 2014; Published 5 March 2014

Academic Editors: M. W. Jann and F. M. Mahomoodally

Copyright © 2014 Maryam Hajrezaie et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Metal-based drugs with extensive clinical applications hold great promise for the development of cancer chemotherapeutic agents. In the last few decades, Schiff bases and their complexes have become well known for their extensive biological potential. In the present study, we examined the antiproliferative effect of a copper (II) complex on HT-29 colon cancer cells. The Cu(BrHAP)2 Schiff base compound demonstrated a potent antiproliferative effect in HT-29 cells, with an IC50 value of 2.87 μg/ml after 72 h of treatment. HT-29 cells treated with Cu (II) complexes underwent apoptosis death, as exhibited by a progressive elevation in the proportion of the G1 cell population. At a concentration of 6.25 μg/ml, the Cu(BrHAP)2 compound caused significant elevation in ROS production following perturbation of mitochondrial membrane potential and cytochrome c release, as assessed by the measurement of fluorescence intensity in stained cells. Furthermore, the activation of caspases 3/7 and 9 was part of the Cu (II) complex-induced apoptosis, which confirmed the involvement of mitochondrial-mediated apoptosis. Meanwhile, there was no significant activation of caspase-8. Taken together, these results imply that the Cu(BrHAP)2 compound is a potential candidate for further in vivo and clinical colon cancer studies to develop novel chemotherapeutic agents derived from metal-based agents.