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

doi:10.1016/j.bbrc.2005.01.028

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 journal › Article › peer-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 language	English
Pages (from-to)	623-632
Number of pages	10
Journal	Biochemical and Biophysical Research Communications
Volume	328
Issue number	2
DOIs	https://doi.org/10.1016/j.bbrc.2005.01.028
Publication status	Published - 11 Mar 2005

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title = "Chlorimipramine: a novel anticancer agent with a mitochondrial target",

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.",

author = "Emma Daley and D. Wilkie and A. Loesch and Hargreaves, {I. P.} and Kendall, {D. A.} and Geoff Pilkington and Bates, {Timothy E.}",

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T2 - a novel anticancer agent with a mitochondrial target

AU - Daley, Emma

AU - Wilkie, D.

AU - Loesch, A.

AU - Hargreaves, I. P.

AU - Kendall, D. A.

AU - Pilkington, Geoff

AU - Bates, Timothy E.

PY - 2005/3/11

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N2 - 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.

AB - 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.

U2 - 10.1016/j.bbrc.2005.01.028

DO - 10.1016/j.bbrc.2005.01.028

M3 - Article

SN - 0006-291X

VL - 328

SP - 623

EP - 632

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 2

ER -

Chlorimipramine: a novel anticancer agent with a mitochondrial target

Abstract

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