PPAR gamma ligands sensitize non-small cell lung cancer cells(NSCLC) to ionizing radiation-induced apoptosis

Abstract

We investigated possible radio-sensitizing possible radio-sensitizing acticities of a well known PPAR gamma ligand ciglitazone and novel PPAR gamma ligands CAY10415 and CAY10506 in human non-small lung cancer cells. These three PPAR gamma ligands enhanced ionizing radiation (IR)-induced apoptosis and caspase-3-mediated PARP cleavage. The combined PPAR gamma ligands-IR treatment also triggered caspase-8 activation and this initiator caspase exerted a critical role in the combination-induced apoptosis. In addition, PPAR gamma ligands could also enhanced IR-induced DNA damage response such as ��H2AX. Moreover, the combination treatment significantly increased ROS generation, and ROS scavengers such as NAC, but not Tiron, inhibited the combined treatment-induced ROS generation and apoptotic cell death. Taken together, these results indicate that the combined treatment of PPAR gamma ligands and IR synergistically induced DNA damage and apoptosis, and ROS are critical regulators of these enhanced DNA damage and apoptosis