title: Lysosome Inhibitors Enhance the Chemotherapeutic Activity of Doxorubicin in HepG2 Cells.
abstract: The lysosome inhibitors bafilomycin A1 and chloroquine have both lysosomotropic properties and autophagy inhibition ability, and are promising clinical agents to be used in combination with anticancer drugs. In order to investigate this combination effect, HepG2 cells were treated with bafilomycin A1, chloroquine, or/and doxorubicin, and their proliferative ability, induction of apoptosis, and the changes of lysosomal membrane permeabilization and mitochondrial membrane potential were studied. The results demonstrate that treatment with bafilomycin A1 or chloroquine alone at a relatively low concentration promotes the inhibitory effect of doxorubicin on cell growth and apoptosis. Further studies reveal that bafilomycin A1 and chloroquine promote lysosomal membrane permeabilization and the reduction of mitochondrial membrane potential induced by doxorubicin. Our findings suggest that bafilomycin A1 and chloroquine potentiate the anticancer effect of doxorubicin in hepatic cancer cells and that supplementation of conventional chemotherapy with lysosome inhibitors may provide a more efficient anticancer therapy.
authors.affiliation: School of Biotechnology, Tianjin University of Science and Technology, Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin, China.
authors.forename: Yuyin
authors.initials: Y
authors.lastname: Li
authors.forename: Yuejun
authors.initials: Y
authors.lastname: Sun
authors.forename: Lifang
authors.initials: L
authors.lastname: Jing
authors.forename: Jianjun
authors.initials: J
authors.lastname: Wang
authors.forename: Yali
authors.initials: Y
authors.lastname: Yan
authors.forename: Yajuan
authors.initials: Y
authors.lastname: Feng
authors.forename: Yueying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhenxing
authors.initials: Z
authors.lastname: Liu
authors.forename: Long
authors.initials: L
authors.lastname: Ma
authors.forename: Aipo
authors.initials: A
authors.lastname: Diao
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002738:Chloroquine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D004357:Drug Synergism; D056945:Hep G2 Cells; D006801:Humans; D008247:Lysosomes / Q000187:drug effects* / Q000502:physiology; D018942:Macrolides / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D018942:Macrolides; D004317:Doxorubicin; D002738:Chloroquine; C040929:bafilomycin A1