The effect of KNK437, a heat shock protein inhibitor, on angiogenesis of endothelial cells

Aim: Hyperthermia is an effective therapy for cancer and tumor angiogenesis. However, the development of thermotolerance is an important problem. We aimed to investigate the effects of KNK437 and quercetin on angiogenesis and thermotolerance in endothelial cells (ECs). Materials and methods: ECs were grown in EGM-2 medium. ECs were preincubated with KNK437 or quercetin and then treated with single and fractionated hyperthermia. Tube formation assay on Matrigel Matrix was performed in these cells to investigate angiogenesis. Results: Tube formation was suppressed in cells that were treated with KNK437 and quercetin at 37 °C. Single hyperthermia (45 °C for 1 h) inhibited tube formation. KNK437 and quercetin pretreatment decreased capillary-like structures more effectively than single hyperthermia treatment. In cells that acquired thermotolerance induced by fractionated hyperthermia, tube formation was dramatically increased, but KNK437 and quercetin reversed the eff ects of thermotolerance on angiogenesis. KNK437 was found to be more effective than quercetin in all study groups. Conclusion: This study is original in that KNK437 inhibited angiogenesis and thermotolerance in ECs. Th is compound may be an essential molecule contributing to the efficient treatment of hyperthermic therapy in human cancers.