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Dihydrocelastrol induces cell death and suppresses angiogenesis through BCR/AP-1/junb signalling in diffuse large B cell lymphoma.
Lai, Yue; Guo, Shushan; Tang, Qiongwei; Chang, Gaomei; Zhang, Hui; Li, Bo; Feng, Qilin; Hu, Ke; Xu, Zhijian; Gao, Xuejie; Zhang, Qikai; Yi, Hongfei; Song, Dongliang; Zhang, Yifei; Peng, Yu; Cai, Haiyan; Zhu, Weiliang; Shi, Jumei.
Afiliación
  • Lai Y; Department of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
  • Guo S; Department of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
  • Tang Q; Department of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
  • Chang G; Department of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
  • Zhang H; Department of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
  • Li B; State Key Laboratory of Drug Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Feng Q; Department of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
  • Hu K; Department of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
  • Xu Z; State Key Laboratory of Drug Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Gao X; Department of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
  • Zhang Q; Department of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
  • Yi H; Department of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
  • Song D; Department of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
  • Zhang Y; Department of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
  • Peng Y; Department of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
  • Cai H; Department of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
  • Zhu W; State Key Laboratory of Drug Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. Electronic address: wlzhu@simm.ac.cn.
  • Shi J; Department of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China. Electronic address: shijumei@tongji.edu.cn.
Arch Biochem Biophys ; 754: 109929, 2024 04.
Article en En | MEDLINE | ID: mdl-38367794
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Linfoma de Células B Grandes Difuso / Factor de Transcripción AP-1 / Triterpenos Pentacíclicos Límite: Humans Idioma: En Revista: Arch Biochem Biophys Año: 2024 Tipo del documento: Article País de afiliación: China
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Linfoma de Células B Grandes Difuso / Factor de Transcripción AP-1 / Triterpenos Pentacíclicos Límite: Humans Idioma: En Revista: Arch Biochem Biophys Año: 2024 Tipo del documento: Article País de afiliación: China