Dihydrocelastrol induces cell death and suppresses angiogenesis through BCR/AP-1/junb signalling in diffuse large B cell lymphoma.

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Although treatment options have improved, a large proportion of patients show low survival rates, highlighting an urgent need for novel therapeutic strategies. The aim of this study was to investigate the efficacy of the new small-molecule compound dihydrocelastrol (DHCE), acquired through the structural modification of celastrol (CE), in the treatment of DLBCL. DHCE showed potent anti-lymphoma efficacy and synergistic effects with doxorubicin. DHCE triggered DLBCL cell apoptosis and G0/G1-phase blockade, thereby hindering angiogenesis. DHCE inhibited B-cell receptor cascade signalling and Jun B and p65 nuclear translocation, thereby suppressing pro-tumourigenic signalling. Finally, DHCE exerted lower toxicity than CE, which showed severe hepatic, renal, and reproductive toxicity in vivo. Our findings support further investigation of the clinical efficacy of DHCE against DLBCL.

• Authors: Yue Lai, Shushan Guo, Qiongwei Tang, Gaomei Chang, Hui Zhang, Bo Li, Qilin Feng, Ke Hu, Zhijian Xu, Xuejie Gao, Qikai Zhang, Hongfei Yi, Dongliang Song, Yifei Zhang, Yu Peng, Haiyan Cai, Weiliang Zhu, Jumei Shi
• Journal: Archives of biochemistry and biophysics (Arch Biochem Biophys) Vol. 754 Pg. 109929 (Apr 2024) ISSN: 1096-0384 [Electronic] United States
• PMID: 38367794 (Publication Type: Journal Article)
• Copyright: Copyright © 2024 Elsevier Inc. All rights reserved.

Chemical References

• Transcription Factor AP-1
• celastrol
• Pentacyclic Triterpenes

Topics

• Humans
• Transcription Factor AP-1 (metabolism)
• Angiogenesis
• Signal Transduction
• Apoptosis
• Lymphoma, Large B-Cell, Diffuse (metabolism)
• Cell Line, Tumor
• Cell Proliferation
• Pentacyclic Triterpenes