Si Hyoung Kim1, Hae-Young Shin2, Yong-Sun Kim3, Jun Goo Kang1, Chul Sik Kim1, Sung-Hee Ihm1, Moon Gi Choi1, Hyung Joon Yoo1, Seong Jin Lee4. 1. Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon, Republic of Korea. 2. Ilsong Institute of Life Science, Gyeonggi-Do, Republic of Korea. 3. Ilsong Institute of Life Science, Gyeonggi-Do, Republic of Korea Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Republic of Korea. 4. Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon, Republic of Korea leesj@hallym.ac.kr.
Abstract
BACKGROUND/AIM: 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. MATERIALS AND 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. CONCLUSION: 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). Copyright
BACKGROUND/AIM: 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. MATERIALS AND 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. CONCLUSION: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). Copyright