Z-FY-CHO (10 µM, for 1 h) pretreatment alleviated cell death induced by 6-OHDA. Z-FY-CHO inhibits the increase in CTSL protein expression in 6-OHDA-treated SH-SY5Y cells. Treatment with Z-FY-CHO caused more LC3-II and less P62 expression in SH-SY5Y cells treated with 6-OHDA, indicating enhancing autophagy activity, and Z-FY-CHO blocks activation of caspase-3 and PARP.
Treatment with the specific cathepsin L inhibitor Z-FY-CHO (10 μM) or transfection with cathepsin L shRNA significantly increased the radiosensitivity of U251 cells. Both suppression and knockdown of cathepsin L in U251 cells increased irradiation-induced DNA damage and G2/M phase cell cycle arrest. Both suppression and knockdown of cathepsin L in U251 cells also increased irradiation-induced apoptosis, as shown by the increased levels of Bax and decreased levels of Bcl-2.