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EBioMedicine. 2016 Jul;9:130-139. doi: 10.1016/j.ebiom.2016.06.013. Epub 2016 Jun 7.

Repurposing Cationic Amphiphilic Antihistamines for Cancer Treatment.

Author information

1
Cell Death & Metabolism, Center for Autophagy, Recycling and Disease, Danish Cancer Society Research Center, DK-2100 Copenhagen, Denmark.
2
Statistics, Bioinformatics & Registry, Danish Cancer Society Research Center, DK-2100 Copenhagen, Denmark.
3
Department of Veterinary Disease Biology, Section for Molecular Disease Biology, Faculty of Health and Medical Sciences, Copenhagen University, DK-2100 Copenhagen, Denmark.
4
Department of Oncology, Copenhagen University Hospital Herlev, DK-2730 Herlev, Denmark.
5
Department of Oncology, Copenhagen University Hospital Rigshospitalet, DK-2200 DK-2730 Copenhagen, Denmark.
6
Cell Death & Metabolism, Center for Autophagy, Recycling and Disease, Danish Cancer Society Research Center, DK-2100 Copenhagen, Denmark. Electronic address: mj@cancer.dk.

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.

PMID:
27333030
PMCID:
PMC4972561
DOI:
10.1016/j.ebiom.2016.06.013
[Indexed for MEDLINE]
Free PMC Article

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