Chlorimipramine: a novel anticancer agent with a mitochondrial target

Daley, E. and Wilkie, D. and Loesch, A. and Hargreaves, I. P. and Kendall, D. A. and Pilkington, G. J. and Bates, T. E. (2005) Chlorimipramine: a novel anticancer agent with a mitochondrial target. Biochemical and Biophysical Research Communications, 328 (2). pp. 623-632. ISSN 0006-291X

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Full text URL: http://dx.doi.org/10.1016/j.bbrc.2005.01.028

Abstract

Mitochondria have been suggested to be a potential intracellular target for cancer chemotherapy. In this report, we demonstrate the ability of the tricyclic antidepressant chlorimipramine to kill human glioma cells in vitro by a molecular mechanism resulting in an increase in caspase 3 activity following inhibition of glioma oxygen consumption. Studies with isolated rat mitochondria showed that chlorimipramine specifically inhibited mitochondrial complex III activity, which causes decreased mitochondrial membrane potential as well as mitochondrial swelling and vacuolation. The use of chlorimipramine in human as an effective, non-toxic cancer therapeutic having a strong selectivity between cancer cells and normal cells on the basis of their mitochondrial function is discussed.

Item Type:Article
Additional Information:Mitochondria have been suggested to be a potential intracellular target for cancer chemotherapy. In this report, we demonstrate the ability of the tricyclic antidepressant chlorimipramine to kill human glioma cells in vitro by a molecular mechanism resulting in an increase in caspase 3 activity following inhibition of glioma oxygen consumption. Studies with isolated rat mitochondria showed that chlorimipramine specifically inhibited mitochondrial complex III activity, which causes decreased mitochondrial membrane potential as well as mitochondrial swelling and vacuolation. The use of chlorimipramine in human as an effective, non-toxic cancer therapeutic having a strong selectivity between cancer cells and normal cells on the basis of their mitochondrial function is discussed.
Keywords:chlorimipramine, clomipramine, anticancer, cancer, glioma, antidepressants, tricyclic, apoptosis
Subjects:A Medicine and Dentistry > A100 Pre-clinical Medicine
B Subjects allied to Medicine > B200 Pharmacology, Toxicology and Pharmacy
B Subjects allied to Medicine > B140 Neuroscience
A Medicine and Dentistry > A300 Clinical Medicine
Divisions:College of Science > School of Life Sciences
ID Code:5225
Deposited By: Timothy Bates
Deposited On:27 Jun 2012 16:45
Last Modified:27 Jun 2012 16:45

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