Unknown

Dataset Information

0

Thapsigargin sensitizes human esophageal cancer to TRAIL-induced apoptosis via AMPK activation.

ABSTRACT: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent for esophageal squamous cell carcinoma (ESCC). Forced expression of CHOP, one of the key downstream transcription factors during endoplasmic reticulum (ER) stress, upregulates the death receptor 5 (DR5) levels and promotes oxidative stress and cell death. In this study, we show that ER stress mediated by thapsigargin promoted CHOP and DR5 synthesis thus sensitizing TRAIL treatment, which induced ESCC cells apoptosis. These effects were reversed by DR5 siRNA in vitro and CHOP siRNA both in vitro and in vivo. Besides, chemically inhibition of AMPK by Compound C and AMPK siRNA weakened the anti-cancer effect of thapsigargin and TRAIL co-treatment. Therefore, our findings suggest ER stress effectively sensitizes human ESCC to TRAIL-mediated apoptosis via the TRAIL-DR5-AMPK signaling pathway, and that activation of ER stress may be beneficial for improving the efficacy of TRAIL-based anti-cancer therapy.

SUBMITTER: Ma Z 

PROVIDER: S-EPMC5059685 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Thapsigargin sensitizes human esophageal cancer to TRAIL-induced apoptosis via AMPK activation.

Ma Zhiqiang Z   Fan Chongxi C   Yang Yang Y   Di Shouyin S   Hu Wei W   Li Tian T   Zhu Yifang Y   Han Jing J   Xin Zhenlong Z   Wu Guiling G   Zhao Jing J   Li Xiaofei X   Yan Xiaolong X  

Scientific reports 20161012

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent for esophageal squamous cell carcinoma (ESCC). Forced expression of CHOP, one of the key downstream transcription factors during endoplasmic reticulum (ER) stress, upregulates the death receptor 5 (DR5) levels and promotes oxidative stress and cell death. In this study, we show that ER stress mediated by thapsigargin promoted CHOP and DR5 synthesis thus sensitizing TRAIL treatment, which induced ESCC  ...[more]

Similar Datasets

Unknown Bortezomib sensitizes human esophageal squamous cell carcinoma cells to TRAIL-mediated apoptosis via activation of both extrinsic and intrinsic apoptosis pathways.
| S-EPMC2884061 | biostudies-other
Unknown Amiodarone sensitizes human glioma cells but not astrocytes to TRAIL-induced apoptosis via CHOP-mediated DR5 upregulation.
| S-EPMC3064603 | biostudies-literature
Unknown Alternol Sensitizes Renal Carcinoma Cells to TRAIL-Induced Apoptosis.
| S-EPMC8026879 | biostudies-literature
Unknown Ginsenoside compound K sensitizes human colon cancer cells to TRAIL-induced apoptosis via autophagy-dependent and -independent DR5 upregulation.
| S-EPMC5108320 | biostudies-literature
Unknown Curcumin Sensitizes Kidney Cancer Cells to TRAIL-Induced Apoptosis via ROS Mediated Activation of JNK-CHOP Pathway and Upregulation of DR4.
| S-EPMC7284747 | biostudies-literature
Unknown Low-dose anisomycin sensitizes melanoma cells to TRAIL induced apoptosis.
| S-EPMC3571996 | biostudies-literature
Unknown Modulation of Mcl-1 sensitizes glioblastoma to TRAIL-induced apoptosis.
| S-EPMC3938842 | biostudies-other
Unknown Cyclopamine sensitizes multiple myeloma cells to circularly permuted TRAIL-induced apoptosis.
| S-EPMC7905534 | biostudies-literature
Unknown Bufalin sensitizes human bladder carcinoma cells to TRAIL-mediated apoptosis.
| S-EPMC5494769 | biostudies-other
Unknown Andrographolide sensitizes human renal carcinoma cells to TRAIL‑induced apoptosis through upregulation of death receptor 4.
| S-EPMC7551412 | biostudies-literature