Heat Shock Protein translocation induced by membrane fluidization increases tumor-cell sensitivity to chemotherapeutic drugs.
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.
Dempsey
Nina C
NC
Chester Centre for Stress Research, University of Chester, United Kingdom.
Ireland
H Elyse
HE
Smith
Carly M
CM
Hoyle
Christine F
CF
Williams
John H H
JH
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
D000970:Antineoplastic Agents; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D053148:Caspase 3