Daley, E., Wilkie, D., Loesch, A. , Hargreaves, I. P., Kendall, D. A., 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
Full content URL: http://dx.doi.org/10.1016/j.bbrc.2005.01.028
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Item Type: | Article |
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Item Status: | Live Archive |
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.
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. |
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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 On: | 27 Jun 2012 16:45 |
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