title: Heat Shock Protein translocation induced by membrane fluidization increases tumor-cell sensitivity to chemotherapeutic drugs.
abstract: Treatment of chronic lymphocytic leukemia (CLL) remains a challenge due to the frequency of drug resistance amongst patients. Improving the delivery of chemotherapeutic agents while reducing the expression of anti-apoptotic Heat Shock Proteins (HSPs) within the cancer cells may facilitate in overcoming this drug resistance. We demonstrate for the first time that sub-lethal doses of chemotherapeutic agents can be combined with membrane fluidizing treatments to produce a significant increase in drug efficacy and apoptosis in vitro. We show that fluidizers result in a transient decrease in intracellular HSPs, resulting in increased tumor-cell sensitivity and a membrane-associated induction of HSP gene expression.
authors.affiliation: Chester Centre for Stress Research, University of Chester, United Kingdom.
authors.forename: Nina C
authors.initials: NC
authors.lastname: Dempsey
authors.forename: H Elyse
authors.initials: HE
authors.lastname: Ireland
authors.forename: Carly M
authors.initials: CM
authors.lastname: Smith
authors.forename: Christine F
authors.initials: CF
authors.lastname: Hoyle
authors.forename: John H H
authors.initials: JH
authors.lastname: Williams
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000502:physiology*; D019008:Drug Resistance, Neoplasm; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000378:metabolism; D007962:Leukocytes / Q000502:physiology; D008560:Membrane Fluidity / Q000502:physiology; D016133:Polymerase Chain Reaction; D021381:Protein Transport
chemical_list: D000970:Antineoplastic Agents; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D053148:Caspase 3