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Biochem Biophys Res Commun. 2005 Mar 11;328(2):623-32.

Chlorimipramine: a novel anticancer agent with a mitochondrial target.

Author information

1
Experimental Neuro-oncology Group, Department of Neuropathology, Institute of Psychiatry, King's College London, London SE5 8AF, UK.

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.

PMID:
15694394
DOI:
10.1016/j.bbrc.2005.01.028
[Indexed for MEDLINE]

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