title: Tunicamycin induces paraptosis potentiated by inhibition of BRAFV600E in FRO anaplastic thyroid carcinoma cells.
abstract: OBJECTIVE
  The aim of the present study was to elucidate whether tunicamycin (TM) induces paraptosis as a cell death subroutine in anaplastic thyroid carcinoma (ATC) cells.
  
  
  METHODS
  8505C, CAL62 and FRO cells were used. After treatment of TM, cell survival and morphology were investigated. The effect of the BRAF(V600E) inhibitor PLX4032 in combination with TM was evaluated.
  
  
  RESULTS
  In FRO cells, TM induced paraptosis characteristic of cytoplasmic vacuolation and endoplasmic reticulum (ER) swelling, which was not associated with caspase activation and ER stress. TM-induced paraptosis was ameliorated by pre-treatment with the translation inhibitor cycloheximide, while it was accelerated by pre-treatment with the proteasome inhibitor MG132. PLX4032 augmented TM-induced paraptosis.
  
  
  CONCLUSIONS
  TM induces paraptosis relevant to de novo protein synthesis and proteasomal activity, and inhibition of BRAF(V600E) potentiates TM-induced paraptosis in FRO cells harboring BRAF(V600E).
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: Ilsong Institute of Life Science, Gyeonggi-Do, Republic of Korea.
authors.forename: Hae-Young
authors.initials: HY
authors.lastname: Shin
authors.affiliation: Ilsong Institute of Life Science, Gyeonggi-Do, Republic of Korea Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Republic of Korea.
authors.forename: Yong-Sun
authors.initials: YS
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 leesj@hallym.ac.kr.
authors.forename: Seong Jin
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D059865:Endoplasmic Reticulum Stress; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D009154:Mutation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D014176:Protein Biosynthesis; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D065646:Thyroid Carcinoma, Anaplastic; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014415:Tunicamycin / Q000494:pharmacology*; D000077484:Vemurafenib
chemical_list: D007211:Indoles; D013449:Sulfonamides; D014415:Tunicamycin; D000077484:Vemurafenib; D048493:Proto-Oncogene Proteins B-raf; D020169:Caspases; D046988:Proteasome Endopeptidase Complex
keywords: Anaplastic thyroid carcinoma; BRAF; paraptosis; tunicamycin