The Novel Vascular Disrupting Agent ANG501 Induces Cell Cycle Arrest and Enhances Endothelial Cell Sensitivity to Radiation

摘要: The efficacy of approaches in which vascular disrupting agents (VDA) are used combination with conventional chemotherapy and/or radiation therapy the treatment cancer might be improved if there were a better understanding cellular and molecular changes induced normal malignant cells as result VDA exposure. Toward this goal, murine endothelial treated vitro ANG501, novel stilbene developed our laboratory, alterations gene expression determined by genome-wide microarray analysis subsequently confirmed Western blot analysis. Among genes that shown to upon brief exposure non-cytotoxic doses ANG501 several involved control cell cycle progression apoptosis, including p21Waf1 heat shock/stress proteins hsp25, hsp70 anti-B-crystallin. Reflecting such induction, functional studies cycling is temporarily inhibited following majority accumulate at radiation-sensitive G2/M phase 6 hr. effects transient 24 hr had largely resumed. Combination experiments previously more readily killed radiation. Importantly, significant evident clinically relevant doses. Taken together these findings emphasize need consider radiosensitizing activity VDAs when developing therapies promising compounds