ver-155008 and benzyloxycarbonylvalyl-alanyl-aspartyl-fluoromethyl-ketone

In this study, we evaluated the effect of the hsp70 inhibitor VER155008 on survival of anaplastic thyroid carcinoma (ATC) cells. In ATC cells, VER155008 increased the percentages of dead cells and vacuolated cells. VER155008 did not lead to the cleavage of caspase-3 protein regardless of pretreatment with z-VAD-fmk. VER155008 increased LC3-II protein levels but the protein levels were not changed by autophagy inhibitors. VER155008 caused the dilatation of endoplasmic reticulum (ER), and the increased mRNA levels of Bip and CHOP, suggesting paraptosis. VER155008-induced paraptosis was attenuated by pretreatment with cycloheximide. In conclusion, VER155008 induces paraptosis characterized by cytoplasmic vacuolation, independence of caspase, dilatation of ER and induction of ER stress markers in ATC cells. Moreover, VER155008-induced paraptosis requires de novo protein synthesis in ATC cells.

Topics: Amino Acid Chloromethyl Ketones; Apoptosis; Autophagy; Caspase 3; Caspase Inhibitors; Cell Line, Tumor; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Heat-Shock Proteins; HSP70 Heat-Shock Proteins; Humans; Microscopy, Electron, Transmission; Neoplasm Proteins; Purine Nucleosides; RNA, Messenger; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms; Transcription Factor CHOP; Vacuoles