Repurposing Cationic Amphiphilic Antihistamines for Cancer Treatment

Anne-Marie Ellegaard; Christian Dehlendorff; Anna C. Vind; Atul Anand; Luise Cederkvist; Nikolaj H. T. Petersen; Jesper Nylandsted; Jan Stenvang; Anders Mellemgaard; Kell Osterlind; Soren Friis; Marja Jaattela

doi:10.1016/j.ebiom.2016.06.013

Repurposing Cationic Amphiphilic Antihistamines for Cancer Treatment

Anne-Marie Ellegaard, Christian Dehlendorff, Anna C. Vind, Atul Anand, Luise Cederkvist, Nikolaj H. T. Petersen, Jesper Nylandsted, Jan Stenvang, Anders Mellemgaard, Kell Osterlind, Soren Friis, Marja Jaattela

43 Citations (Scopus)

Abstract

Non-small cell lung cancer (NSCLC) is one of the deadliest cancers worldwide. In search for new NSCLC treatment options, we screened a cationic amphiphilic drug (CAD) library for cytotoxicity against NSCLC cells and identified several CAD antihistamines as inducers of lysosomal cell death. We then performed a cohort study on the effect of CAD antihistamine use on mortality of patients diagnosed with non-localized cancer in Denmark between 1995 and 2011. The use of the most commonly prescribed CAD antihistamine, loratadine, was associated with significantly reduced all-cause mortality among patients with non-localized NSCLC or any non-localized cancer when compared with use of non-CAD antihistamines and adjusted for potential confounders. Of the less frequently described CAD antihistamines, astemizole showed a similar significant association with reduced mortality as loratadine among patients with any non-localized cancer, and ebastine use showed a similar tendency. The association between CAD antihistamine use and reduced mortality was stronger among patients with records of concurrent chemotherapy than among those without such records. In line with this, sub-micromolar concentrations of loratadine, astemizole and ebastine sensitized NSCLC cells to chemotherapy and reverted multidrug resistance in NSCLC, breast and prostate cancer cells. Thus, CAD antihistamines may improve the efficacy of cancer chemotherapy

Original language	English
Journal	EBioMedicine
Volume	9
Pages (from-to)	130-139
Number of pages	10
ISSN	2352-3964
DOIs	https://doi.org/10.1016/j.ebiom.2016.06.013
Publication status	Published - Jul 2016

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@article{8156b0ef8adb423692577e86467ce8b7,

title = "Repurposing Cationic Amphiphilic Antihistamines for Cancer Treatment",

abstract = "Non-small cell lung cancer (NSCLC) is one of the deadliest cancers worldwide. In search for new NSCLC treatment options, we screened a cationic amphiphilic drug (CAD) library for cytotoxicity against NSCLC cells and identified several CAD antihistamines as inducers of lysosomal cell death. We then performed a cohort study on the effect of CAD antihistamine use on mortality of patients diagnosed with non-localized cancer in Denmark between 1995 and 2011. The use of the most commonly prescribed CAD antihistamine, loratadine, was associated with significantly reduced all-cause mortality among patients with non-localized NSCLC or any non-localized cancer when compared with use of non-CAD antihistamines and adjusted for potential confounders. Of the less frequently described CAD antihistamines, astemizole showed a similar significant association with reduced mortality as loratadine among patients with any non-localized cancer, and ebastine use showed a similar tendency. The association between CAD antihistamine use and reduced mortality was stronger among patients with records of concurrent chemotherapy than among those without such records. In line with this, sub-micromolar concentrations of loratadine, astemizole and ebastine sensitized NSCLC cells to chemotherapy and reverted multidrug resistance in NSCLC, breast and prostate cancer cells. Thus, CAD antihistamines may improve the efficacy of cancer chemotherapy",

author = "Anne-Marie Ellegaard and Christian Dehlendorff and Vind, {Anna C.} and Atul Anand and Luise Cederkvist and Petersen, {Nikolaj H. T.} and Jesper Nylandsted and Jan Stenvang and Anders Mellemgaard and Kell Osterlind and Soren Friis and Marja Jaattela",

year = "2016",

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doi = "10.1016/j.ebiom.2016.06.013",

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AU - Ellegaard, Anne-Marie

AU - Dehlendorff, Christian

AU - Vind, Anna C.

AU - Anand, Atul

AU - Cederkvist, Luise

AU - Petersen, Nikolaj H. T.

AU - Nylandsted, Jesper

AU - Stenvang, Jan

AU - Mellemgaard, Anders

AU - Osterlind, Kell

AU - Friis, Soren

AU - Jaattela, Marja

PY - 2016/7

Y1 - 2016/7

N2 - Non-small cell lung cancer (NSCLC) is one of the deadliest cancers worldwide. In search for new NSCLC treatment options, we screened a cationic amphiphilic drug (CAD) library for cytotoxicity against NSCLC cells and identified several CAD antihistamines as inducers of lysosomal cell death. We then performed a cohort study on the effect of CAD antihistamine use on mortality of patients diagnosed with non-localized cancer in Denmark between 1995 and 2011. The use of the most commonly prescribed CAD antihistamine, loratadine, was associated with significantly reduced all-cause mortality among patients with non-localized NSCLC or any non-localized cancer when compared with use of non-CAD antihistamines and adjusted for potential confounders. Of the less frequently described CAD antihistamines, astemizole showed a similar significant association with reduced mortality as loratadine among patients with any non-localized cancer, and ebastine use showed a similar tendency. The association between CAD antihistamine use and reduced mortality was stronger among patients with records of concurrent chemotherapy than among those without such records. In line with this, sub-micromolar concentrations of loratadine, astemizole and ebastine sensitized NSCLC cells to chemotherapy and reverted multidrug resistance in NSCLC, breast and prostate cancer cells. Thus, CAD antihistamines may improve the efficacy of cancer chemotherapy

AB - Non-small cell lung cancer (NSCLC) is one of the deadliest cancers worldwide. In search for new NSCLC treatment options, we screened a cationic amphiphilic drug (CAD) library for cytotoxicity against NSCLC cells and identified several CAD antihistamines as inducers of lysosomal cell death. We then performed a cohort study on the effect of CAD antihistamine use on mortality of patients diagnosed with non-localized cancer in Denmark between 1995 and 2011. The use of the most commonly prescribed CAD antihistamine, loratadine, was associated with significantly reduced all-cause mortality among patients with non-localized NSCLC or any non-localized cancer when compared with use of non-CAD antihistamines and adjusted for potential confounders. Of the less frequently described CAD antihistamines, astemizole showed a similar significant association with reduced mortality as loratadine among patients with any non-localized cancer, and ebastine use showed a similar tendency. The association between CAD antihistamine use and reduced mortality was stronger among patients with records of concurrent chemotherapy than among those without such records. In line with this, sub-micromolar concentrations of loratadine, astemizole and ebastine sensitized NSCLC cells to chemotherapy and reverted multidrug resistance in NSCLC, breast and prostate cancer cells. Thus, CAD antihistamines may improve the efficacy of cancer chemotherapy

U2 - 10.1016/j.ebiom.2016.06.013

DO - 10.1016/j.ebiom.2016.06.013

M3 - Journal article

C2 - 27333030

SN - 2352-3964

VL - 9

SP - 130

EP - 139

JO - EBioMedicine

JF - EBioMedicine

ER -

Repurposing Cationic Amphiphilic Antihistamines for Cancer Treatment

Abstract

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