Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon, Republic of Korea.
Ilsong Institute of Life Science, Gyeonggi-Do, Republic of Korea.
Anticancer Res. 2014 Sep;34(9):4857-68.
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.
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.
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.
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).
背景/目的：本研究旨在阐明衣霉素（TM）是否通过凋亡小体程序诱导甲状腺未分化癌（ATC）细胞死亡。
使用 8505C、CAL62 和 FRO 细胞。用 TM 处理后，观察细胞存活和形态。评估 BRAF(V600E)抑制剂 PLX4032 与 TM 的联合作用。
在 FRO 细胞中，TM 诱导具有细胞质空泡化和内质网（ER）肿胀特征的凋亡小体，这与半胱天冬酶激活和 ER 应激无关。用翻译抑制剂环己酰亚胺预处理可减轻 TM 诱导的凋亡小体，而用蛋白酶体抑制剂 MG132 预处理可加速 TM 诱导的凋亡小体。PLX4032 增强了 TM 诱导的 FRO 细胞中 BRAF(V600E) 存在的凋亡小体。
TM 诱导与从头蛋白质合成和蛋白酶体活性相关的凋亡小体，抑制 BRAF(V600E) 增强了 FRO 细胞中 TM 诱导的凋亡小体。
