University of Kentucky
In Vitro Dual Treatment of Cancer Cells with Hsp90 Inhibitors and Hyperthermia
Institution
University of Kentucky
Faculty Advisor/ Mentor
J. Zach Hilt; Kim Anderson
Abstract
Successful hyperthermia therapy of cancer is dependent upon the extent of heat-induced protein denaturation and aggregation within the cell.¹ When a cell is presented with potentially toxic conditions, such as hyperthermia, heat shock proteins (Hsps) ensure cell survival by re-folding damaged proteins.² Hsp90, the most abundant heat shock protein within eukaryotic cells, has been shown to induce thermotolerance during hyperthermia therapy by stabilizing numerous client proteins.³ In this research, the effects of Hsp90 inhibitors, geldanamycin (GA) and 17-Nallylamino-17-demethoxygeldanamycin (17-AAG), in combination with hyperthermia therapy on cancer cell viability was examined. In an in vitro study, cultured human A549 lung carcinoma cells were exposed to non-toxic concentrations of inhibitors for 48 h followed by a 30 min hyperthermia treatment. A hyperthermic temperature of 43°C was created via temperaturecontrolled incubation or alternating magnetic field activation of non-toxic, citric acid coated Fe₃O₄ nanoparticles (magnetic fluid hyperthermia). Our results suggested that the Hsp90 inhibitors do not enhance the effects of hyperthermia, and possible explanations have been proposed.
In Vitro Dual Treatment of Cancer Cells with Hsp90 Inhibitors and Hyperthermia
Successful hyperthermia therapy of cancer is dependent upon the extent of heat-induced protein denaturation and aggregation within the cell.¹ When a cell is presented with potentially toxic conditions, such as hyperthermia, heat shock proteins (Hsps) ensure cell survival by re-folding damaged proteins.² Hsp90, the most abundant heat shock protein within eukaryotic cells, has been shown to induce thermotolerance during hyperthermia therapy by stabilizing numerous client proteins.³ In this research, the effects of Hsp90 inhibitors, geldanamycin (GA) and 17-Nallylamino-17-demethoxygeldanamycin (17-AAG), in combination with hyperthermia therapy on cancer cell viability was examined. In an in vitro study, cultured human A549 lung carcinoma cells were exposed to non-toxic concentrations of inhibitors for 48 h followed by a 30 min hyperthermia treatment. A hyperthermic temperature of 43°C was created via temperaturecontrolled incubation or alternating magnetic field activation of non-toxic, citric acid coated Fe₃O₄ nanoparticles (magnetic fluid hyperthermia). Our results suggested that the Hsp90 inhibitors do not enhance the effects of hyperthermia, and possible explanations have been proposed.