Inhibition of eEF-2 kinase sensitizes human glioma cells to TRAIL and down-regulates Bcl-xL expression

Related Experiment Video

Updated: May 29, 2026

Flow Cytometry-based Drug Screening System for the Identification of Small Molecules That Promote Cellular Differentiation of Glioblastoma Stem Cells
10:28

Flow Cytometry-based Drug Screening System for the Identification of Small Molecules That Promote Cellular Differentiation of Glioblastoma Stem Cells

Published on: January 10, 2018

Yi Zhang1, Yan Cheng, Li Zhang

  • 1Department of Pharmacology and The Penn State Hershey Cancer Institute, The Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, USA. zhangyi@suda.edu.cn

Biochemical and Biophysical Research Communications
|September 28, 2011
PubMed

Insights

Inhibiting elongation factor-2 kinase (eEF-2 kinase) enhances TRAIL therapy efficacy in glioma. This approach sensitizes tumor cells by down-regulating Bcl-xL, offering a potential new strategy for brain cancer treatment.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Elongation factor-2 kinase (eEF-2 kinase) is a calcium/calmodulin-dependent enzyme regulating protein synthesis.
  • eEF-2 kinase activity is elevated in malignancies like gliomas and influences tumor cell responses to therapy.
  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a targeted therapy inducing cancer cell apoptosis with minimal toxicity to normal cells.

Purpose of the Study:

  • To investigate if eEF-2 kinase expression impacts glioma cell sensitivity to TRAIL therapy.
  • To explore the mechanism by which eEF-2 kinase inhibition affects TRAIL-induced apoptosis.

Main Methods:

  • Utilized RNA interference (RNAi) to inhibit eEF-2 kinase expression.
  • Employed a pharmacological inhibitor (NH125) for eEF-2 kinase.
  • Assessed apoptosis induction in human glioma cells treated with TRAIL, alone or in combination with eEF-2 kinase inhibition.
  • Analyzed the expression levels of the anti-apoptotic protein Bcl-xL.
  • Investigated the effect of Bcl-xL overexpression on TRAIL sensitivity.

Main Results:

  • Inhibition of eEF-2 kinase, via RNAi or NH125, significantly enhanced TRAIL-induced apoptosis in human glioma cells.
  • This sensitization was associated with a decrease in the expression of the anti-apoptotic protein Bcl-xL.
  • Overexpression of Bcl-xL counteracted the sensitizing effect of eEF-2 kinase inhibition on TRAIL-mediated apoptosis.

Conclusions:

  • Targeting eEF-2 kinase can sensitize malignant glioma cells to TRAIL therapy.
  • The mechanism involves the down-regulation of Bcl-xL, an anti-apoptotic protein.
  • Combining eEF-2 kinase inhibitors with TRAIL may represent a novel therapeutic strategy for glioma.

Related Concept Videos

Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...