Retracted: Lestaurtinib potentiates TRAIL‐induced apoptosis in glioma via CHOP‐dependent DR5 induction

Abstract

Lestaurtinib, also called CEP‐701, is an inhibitor of tyrosine kinase, causes haematological remission in patients with AML possessing FLT3‐ITD ( FLT3 gene) internal tandem duplication and strongly inhibits tyrosine kinase FLT3. Treatment with lestaurtinib modulates various signalling pathways and leads to cell growth arrest and programmed cell death in several tumour types. However, the effect of lestaurtinib on glioma remains unclear. In this study, we examined lestaurtinib and TRAIL interactions in glioma cells and observed their synergistic activity on glioma cell apoptosis. While U87 and U251 cells showed resistance to TRAIL single treatment, they were sensitized to apoptosis induced by TRAIL in the presence of lestaurtinib because of increased death receptor 5 (DR5) levels through CHOP‐dependent manner. We also demonstrated using a xenograft model of mouse that the tumour growth was absolutely suppressed because of the combined treatment compared to TRAIL or lestaurtinib treatment carried out singly. Our findings reveal a potential new strategy to improve antitumour activity induced by TRAIL in glioma cells using lestaurtinib through a mechanism dependent on CHOP.

Bixin Prevents Colorectal Cancer Development through AMPK-Activated Endoplasmic Reticulum Stress

“…TRAIL, an endogenous cytokine belonging to the tumor necrosis factor superfamily, induces a caspase 8-dependent process of apoptosis in malignant cells, rather than in normal cells [ 22 ]. However, many tumor types present resistance to TRAIL-mediated apoptosis, which restricts its clinical application [ 23 , 24 ]. The combination of Bixin with TRAIL showed a stronger proapoptotic effect than Bixin or TRAIL administered individually, indicating the Bixin ability to increase sensitivity to TRAIL of CRC cells.…”

ASPP2 promotes cell apoptosis in cervical cancer through inhibiting autophagy

“…TRAIL is a signaling molecule involved in the regulation of apoptosis, as well as being a type II transmembrane protein, which can interact with DRs, thereby activating the caspase cascade protease family and inducting apoptosis ( 29 , 30 ). Recent studies have shown that the combination of TRAIL and chemotherapeutic drugs leads to an improvement in the sensitivity of tumor cells to TRAIL.…”

LGK974 Potentiates the Lethality of TRAIL in Hepatocellular Carcinoma Cells by Inducing Apoptosis via Suppressing NF-κB Signaling Pathway

“…Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL), one of Tumor Necrosis Factor (TNF) family members, has been diffusely identified as a hopeful anti-cancer drug to against a large group of tumors because of its selective cytotoxicity to cancer cells [20,21] . After binding to receptors, TRAIL receptor 1 (TRAIL-R1) Death Receptor 4 (DR4) or TRAIL Receptor 2 (TRAIL-R2) Death receptor 5 (DR5), the binding complex recruits the intracellular adaptor Fas Associated Death Domain (FADD) and procaspase 8 to form the Death-Inducing Signaling Complex (DISC), which induces caspase-8 self-cleavage and initiates an extrinsic pathway of apoptosis [22][23][24] .…”