Related Experiment Video
Updated: Dec 16, 2025

An Automated Culture System for Use in Preclinical Testing of Host-Directed Therapies for Tuberculosis
Published on: August 16, 2021
Cladribine Induces ATF4 Mediated Apoptosis and Synergizes with SAHA in Diffuse Large B-Cell Lymphoma Cells
Linyan Xu1,2,3, Jun Jiao1,3, Xiaoshen Sun1,3
1Blood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Abstract:
Cladribine is a purine nucleoside analog used to treat B-cell chronic lymphocytic leukemia and hairy cell leukemia, also functions as an inhibitor of DNA synthesis to block the repair of the damaged DNA. The therapeutic role of cladribine against diffuse large B-cell lymphoma cells (DLBCL) is still undefined. In the present study, we demonstrated that cladribine inhibited cell proliferation and induced G1 phase arrest in human DLBCL cells. Furthermore, we showed that cladribine induced apoptosis by decreasing the expression of c-FLIPL and increasing the expression of DR4 and the cleaved form of caspase8. Cladribine also upregulated the expression of Bax, and downregulated the expression of Mcl-1 and Bcl-2 in a dose-dependent manner. It also activated endoplasmic reticulum (ER) stress, and ATF4 expression was required for cladribine induced apoptosis. Also, we showed that suberoylanilide hydroxamic acid (SAHA) enhanced the pro-apoptotic role of cladribine. Collectively, cladribine activated extrinsic and intrinsic apoptotic signaling pathways via stimulating ER stress signaling pathway and eliciting synergistic effect with SAHA in DLBCL cells.
Related Concept Videos
The Intrinsic Apoptotic Pathway
Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
Targeted Cancer Therapies
There are several types of targeted therapies against...
The Extrinsic Apoptotic Pathway
Tumor Immunotherapy
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF

