title: The hsp70 inhibitor VER155008 induces paraptosis requiring de novo protein synthesis in anaplastic thyroid carcinoma cells.
abstract: 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.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon, Republic of Korea.
authors.forename: Si Hyoung
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon, Republic of Korea.
authors.forename: Jun Goo
authors.initials: JG
authors.lastname: Kang
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon, Republic of Korea.
authors.forename: Chul Sik
authors.initials: CS
authors.lastname: Kim
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon, Republic of Korea.
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Ihm
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon, Republic of Korea.
authors.forename: Moon Gi
authors.initials: MG
authors.lastname: Choi
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon, Republic of Korea.
authors.forename: Hyung Joon
authors.initials: HJ
authors.lastname: Yoo
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon, Republic of Korea. Electronic address: leesj@hallym.ac.kr.
authors.forename: Seong Jin
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors / Q000494:pharmacology; D045744:Cell Line, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006360:Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D046529:Microscopy, Electron, Transmission; D009363:Neoplasm Proteins / Q000096:biosynthesis; D011684:Purine Nucleosides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D065646:Thyroid Carcinoma, Anaplastic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051742:Transcription Factor CHOP / Q000235:genetics; D014617:Vacuoles / Q000187:drug effects / Q000473:pathology
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D009363:Neoplasm Proteins; D011684:Purine Nucleosides; D012333:RNA, Messenger; C550733:VER 155008; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D051742:Transcription Factor CHOP; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: Anaplastic thyroid carcinoma; Hsp70; Paraptosis; Protein synthesis; VER155008