Research article summary (published 30 Aug 2009):

The antipsychotic drug chlorpromazine enhances the cytotoxic effect of tamoxifen in tamoxifen-sensitive and tamoxifen-resistant human breast cancer cells.

Full Abstract

Tamoxifen resistance is a major clinical problem in the treatment of estrogen receptor alpha-positive breast tumors. It is, at present, unclear what exactly causes tamoxifen resistance. For decades, chlorpromazine has been used for treating psychotic diseases, such as schizophrenia. However, the compound is now also recognized as a multitargeting drug with diverse potential applications, for example, it has antiproliferative properties and it can reverse resistance toward antibiotics in bacteria. Furthermore, chlorpromazine can reverse multidrug resistance caused by overexpression of P-glycoprotein in cancer cells. In this study, we have investigated the effect of chlorpromazine on tamoxifen response of human breast cancer cells. We found that chlorpromazine worked synergistically together with tamoxifen with respect to reduction of cell growth and metabolic activity, both in the antiestrogen-sensitive breast cancer cell line, MCF-7, and in a tamoxifen-resistant cell line, established from the MCF-7 cells. Tamoxifen-sensitive and tamoxifen-resistant cells were killed equally well by combined treatment with chlorpromazine and tamoxifen. This synergistic effect could be prevented by addition of estrogen, suggesting that chlorpromazine enhances the effect of tamoxifen through an estrogen receptor-mediated mechanism. To investigate this putative mechanism, we applied biophysical techniques to simple model membranes in the form of unilamellar liposomes of well-defined composition and found that chlorpromazine interacts strongly with lipid bilayers of different composition leading to increased permeability. This implies that chlorpromazine can change influx properties of membranes hence suggesting that chlorpromazine may be a promising chemosensitizing compound for enhancing the cytotoxic effect of tamoxifen.

Author information

Author/s: Yde, Christina W (CW); Clausen, Mathias P (MP); Bennetzen, Martin V (MV); Lykkesfeldt, Anne E (AE); Mouritsen, Ole G (OG); Guerra, Barbara (B);

Affiliation: Department of Biochemistry and Molecular Biology, Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Anti-cancer drugs (Anticancer Drugs), published in England. (Language: eng)

Reference: 2009-Sep; vol 20 (issue 8) : pp 723-35

Dates: Created 2009/07/24; Completed 2009/10/16;

PMID: 19584708, status: MEDLINE (last retrieval date: 10/16/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Binding, Competitive Breast Neoplasms - drug therapy; metabolism; pathology Calorimetry, Differential Scanning Cell Death - drug effects Cell Line, Tumor Chlorpromazine - chemistry; pharmacology Drug Resistance, Neoplasm - drug effects Drug Synergism Estradiol - pharmacology Female

Female Humans Hydrophobicity Permeability Phase Transition Poly(ADP-ribose) Polymerases - metabolism Receptors, Estrogen - metabolism Tamoxifen - pharmacology; toxicity Tumor Stem Cell Assay Unilamellar Liposomes - chemistry

Associated Chemicals: Receptors, Estrogen (0) ; Unilamellar Liposomes (0) ; Tamoxifen (10540-29-1) ; Estradiol (50-28-2) ; Chlorpromazine (50-53-3) ; Poly(ADP-ribose) Polymerases (EC 2.4.2.30)

Related articles

These are the highest related articles currently in the database:

• [Feasibility of estradiol and tamoxifen sensitivity test using contact-sensitive plates for clinical breast carcinoma: preliminary report] 30 Oct 1991
• Kinase-specific phosphorylation of the estrogen receptor changes receptor interactions with ligand, deoxyribonucleic acid, and coregulators associated with alterations in estrogen and tamoxifen activity. 29 Aug 2006
• Cytoplasmic accumulation of the RNA binding protein HuR is central to tamoxifen resistance in estrogen receptor positive breast cancer cells. 21 Sep 2008
• Rapamycin inhibits proliferation of estrogen-receptor-positive breast cancer cells. 13 Nov 2006
• A new marker of tamoxifen resistance of estrogen receptor-positive breast cancer. 27 Feb 2007
• Reversal of tamoxifen resistant breast cancer by low dose estrogen therapy. 30 Jan 2005
• Model systems for the study of estrogen action in tissue culture. 30 Oct 1976
• Long-term exposure to tamoxifen induces hypersensitivity to estradiol. 13 Feb 2004
• EphA2 overexpression decreases estrogen dependence and tamoxifen sensitivity. 13 Jun 2003
• Effect of tamoxifen and 2-methoxyestradiol alone and in combination on human breast cancer cell proliferation. 30 Jan 2003

See 100+ related articles.

Related Article Map

Legend: - FREE Full text Article. - Abstract only. - Title only. More help.

See a large map of 100+ related articles.