title: Inhibition of autophagy and induction of breast cancer cell death by mefloquine, an antimalarial agent.
abstract: Autophagy has been recognized as a potential target for cancer therapy. The antimalarial drug chloroquine (CQ) is able to inhibit autophagy and therefore is being considered for cancer therapeutics. However, the relatively low potency of CQ prompted us to investigate whether other lysosomotropic agents might be more effective, and thus potentially more useful. We therefore compared the cytotoxic efficacy of CQ, the quinoline analog mefloquine (MQ), and the fluoroquinolones ciprofloxacin and levofloxacin in several human breast cancer cell lines. We found that MQ was the most potent compound tested; it inhibited autophagy, triggered endoplasmic reticulum stress, and caused cell death in T47D and MDA-MB-231. Altogether, our study demonstrates superior potency of MQ over CQ and the ability of MQ to produce anticancer effects in both hormone receptor positive and negative breast cancer cell lines, suggesting its usefulness in treating various types of cancer.
authors.affiliation: Department of Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90033, United States.
authors.forename: Natasha
authors.initials: N
authors.lastname: Sharma
authors.forename: Simmy
authors.initials: S
authors.lastname: Thomas
authors.forename: Encouse B
authors.initials: EB
authors.lastname: Golden
authors.forename: Florence M
authors.initials: FM
authors.lastname: Hofman
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Chen
authors.forename: Nicos A
authors.initials: NA
authors.lastname: Petasis
authors.forename: Axel H
authors.initials: AH
authors.lastname: Schönthal
authors.forename: Stan G
authors.initials: SG
authors.lastname: Louie
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000473:pathology*; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015767:Mefloquine / Q000494:pharmacology*; D017239:Paclitaxel / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D054875:Ubiquitination
chemical_list: D000962:Antimalarials; D017239:Paclitaxel; D015767:Mefloquine