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Chlorimipramine: a novel anticancer agent with a mitochondrial target.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2005 Mar 11; Vol. 328 (2), pp. 623-32. - Publication Year :
- 2005
-
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.
- Subjects :
- Animals
Brain Neoplasms drug therapy
Brain Neoplasms metabolism
Brain Neoplasms pathology
Cell Respiration drug effects
Cell Size drug effects
Cell Survival drug effects
Dose-Response Relationship, Drug
Electron Transport Complex III antagonists & inhibitors
Electron Transport Complex III metabolism
Glioma drug therapy
Humans
Male
Membrane Potentials drug effects
Oxygen Consumption drug effects
Rats
Rats, Wistar
Tumor Cells, Cultured
Antineoplastic Agents administration & dosage
Clomipramine administration & dosage
Glioma metabolism
Glioma pathology
Mitochondria drug effects
Mitochondria pathology
Subjects
Details
- Language :
- English
- ISSN :
- 0006-291X
- Volume :
- 328
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 15694394
- Full Text :
- https://doi.org/10.1016/j.bbrc.2005.01.028