Folliculin Deficient Renal Cancer Cells Show Higher Radiosensitivity through Autophagic Cell Death

Purpose: Mutations in the FLCN gene are responsible for fibrofolliculoma, pulmonary and renal cysts, and renal cell carcinoma in patients with Birt-Hogg-Dube syndrome. To explore therapeutic approaches to renal cell carcinoma in patients with Birt-Hogg-Dube syndrome we investigated the anticancer effects of irradiation on folliculin deficient renal cancer cells.Materials and Methods: Folliculin deficient (UOK257 and ACHN-5968) and folliculin expressing (UOK257-2 and ACHN-sc) cell lines were used in this study. Clonogenic assays were used to determine the radiosensitivity of folliculin deficient and expressing renal cell carcinoma cells. Apoptosis was detected in these cells by DAPI and TUNEL assays after irradiation. Monodansylcadaverine analysis, GFP-LC3 assay and Western blot were performed to monitor the autophagic process.Results: Folliculin deficient cells were more sensitive to irradiation than their folliculin expressing counterparts. The enhanced effects of irradiation on folliculin deficient cell...