1. Chester Centre for Stress Research, University of Chester, Parkgate Road, Chester CH1 4BJ, United Kingdom;2. Betsi Cadwaladr University Health Board, Glan Clwyd Hospital, Bodelwyddan, North Wales, LL18 5UJ, United Kingdom
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.