Chlorimipramine: a novel anticancer agent with a mitochondrial target

Emma Daley, D. Wilkie, A. Loesch, I. P. Hargreaves, D. A. Kendall, Geoff Pilkington, Timothy E. Bates

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)623-632
Number of pages10
JournalBiochemical and Biophysical Research Communications
Volume328
Issue number2
DOIs
Publication statusPublished - 11 Mar 2005

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