title: Chloroquine is a zinc ionophore.
abstract: Chloroquine is an established antimalarial agent that has been recently tested in clinical trials for its anticancer activity. The favorable effect of chloroquine appears to be due to its ability to sensitize cancerous cells to chemotherapy, radiation therapy, and induce apoptosis. The present study investigated the interaction of zinc ions with chloroquine in a human ovarian cancer cell line (A2780). Chloroquine enhanced zinc uptake by A2780 cells in a concentration-dependent manner, as assayed using a fluorescent zinc probe. This enhancement was attenuated by TPEN, a high affinity metal-binding compound, indicating the specificity of the zinc uptake. Furthermore, addition of copper or iron ions had no effect on chloroquine-induced zinc uptake. Fluorescent microscopic examination of intracellular zinc distribution demonstrated that free zinc ions are more concentrated in the lysosomes after addition of chloroquine, which is consistent with previous reports showing that chloroquine inhibits lysosome function. The combination of chloroquine with zinc enhanced chloroquine's cytotoxicity and induced apoptosis in A2780 cells. Thus chloroquine is a zinc ionophore, a property that may contribute to chloroquine's anticancer activity.
authors.affiliation: Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America; Department of Radio-Oncology, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xue
authors.affiliation: Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
authors.forename: Amanda
authors.initials: A
authors.lastname: Moyer
authors.affiliation: Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America; Department of Pharmacology, School of Pharmacy, Xuzhou Medical College, Xuzhou, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Peng
authors.affiliation: Department of Radio-Oncology, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, China.
authors.forename: Jinchang
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
authors.forename: Bethany N
authors.initials: BN
authors.lastname: Hannafon
authors.affiliation: Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
authors.forename: Wei-Qun
authors.initials: WQ
authors.lastname: Ding
mesh_terms: D002460:Cell Line; D045744:Cell Line, Tumor; D002738:Chloroquine / Q000737:chemistry* / Q000494:pharmacology*; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D015032:Zinc / Q000737:chemistry*
chemical_list: D005456:Fluorescent Dyes; D002738:Chloroquine; D015032:Zinc