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Berberine derivative DCZ0358 induce oxidative damage by ROS-mediated JNK signaling in DLBCL cells

文献类型：期刊论文

作者Feng, Qilin5; Hu, Ke5; Hu, Huifang5; Lu, Yumeng5; Zhang, Hui5; Wang, Guanli5; Zhang, Qikai5; Xu, Zhijian4; Gao, Xuejie5; Jia, Xinyan5
刊名INTERNATIONAL IMMUNOPHARMACOLOGY
出版日期2023-12-01
卷号125页码:15
ISSN号1567-5769
关键词DLBCL ROS DNA damage JNK Mitochondrial dysfunction
DOI10.1016/j.intimp.2023.111139
通讯作者Li, Bo(boli@simm.ac.cn) ; Zhu, Weiliang(wlzhu@simm.ac.cn) ; Shi, Jumei(shijumei@tongji.edu.cn)
英文摘要The most common neoplasm among adult lymphomas is diffuse large B-cell lymphoma (DLBCL), typically characterized by pain-free and progressive lymph node enlargement. Due to high heterogeneity of DLBCL, 30-40 % of patients are resistant to R-CHOP standard chemoimmunotherapy. DCZ0358 is a new compound designed and synthesized from berberine by our group and the molecular mechanism by which it inhibited DLBCL growth has attracted our widespread attention. In this study, we employed the CCK8 assay to reveal that DCZ0358 inhibited proliferation in a dependent manner of time and dosage of DLBCL cells. Moreover, flowcytometry and western blot results showed that DCZ0358 downregulated the expression of CDK4, CDK6 and CyclinD1 to block cell cycle progression in G0/G1 phase. Furthermore, DCZ0358 enhanced mitochondrial membrane potential depolarization, promoted mitochondrial permeability transport pore openness, increased cytoplastic Ca2+ levels and decreased intracellular adenosine triphosphate production, which led to mitochondrial dysfunction. In particular, DCZ0358 treatment triggered cell apoptosis and elevated intracellular reactive oxygen species (ROS) levels, which subsequently mediated JNK pathway activation. Further research indicated the pre-treatment with ROS scavenger N-acetylcysteine (NAC) and JNK inhibitor SP600125 could partially attenuate apoptosis and DNA damage triggered by DCZ0358. Most importantly, DCZ0358 exhibited synergistic anti-tumor effects when combined with etoposide, a common clinical anti-DLBCL drug, both in vitro and certainly in vivo. Above results demonstrated anti-tumor molecular mechanism of DCZ0358 in DLBCL cells and highlighted the ROS/JNK/DNA damage pathway as a potential target in therapies, which have implications for the development of more effective clinical treatments for DLBCL.
WOS关键词DNA-DAMAGE ; APOPTOSIS ; CANCER ; AUTOPHAGY ; ROS/JNK ; ACTIVATION ; PATHWAYS ; STRESS ; P53
资助项目National Natural Science Foundation of China made significant contributions[82070224] ; National Natural Science Foundation of China made significant contributions[82300225] ; National Natural Science Foundation of China made significant contributions[81971529] ; National Natural Science Foundation of China made significant contributions[82170201] ; National Natural Science Foundation of China made significant contributions[82170190] ; National Natural Science Foundation of China made significant contributions[82170200] ; National Natural Science Foundation of China made significant contributions[22077131] ; Chinese Pharmaceutical Association-Yiling Biopharmaceutical Innovation Project[CPAYLJ201908] ; State Key Laboratory of Natural and Biomimetic Drugs[K202108]
WOS研究方向Immunology ; Pharmacology & Pharmacy
语种英语
出版者ELSEVIER
WOS记录号WOS:001101489100001
源URL[http://119.78.100.183/handle/2S10ELR8/308140]  
专题新药研究国家重点实验室
通讯作者Li, Bo; Zhu, Weiliang; Shi, Jumei
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
2.Tongji Univ, Shanghai East Hosp, Sch Med, Dept Hematol, 150 Jimo Rd, Shanghai 200120, Peoples R China
3.Tongji Univ, Shanghai Peoples Hosp 10, Dept Hematol, Sch Med, Shanghai 200072, Peoples R China
4.Chinese Acad Sci, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
5.Tongji Univ, Shanghai East Hosp, Sch Med, Dept Hematol, Shanghai 200120, Peoples R China
推荐引用方式
GB/T 7714		 Feng, Qilin,Hu, Ke,Hu, Huifang,et al. Berberine derivative DCZ0358 induce oxidative damage by ROS-mediated JNK signaling in DLBCL cells[J]. INTERNATIONAL IMMUNOPHARMACOLOGY,2023,125:15.
APA Feng, Qilin.,Hu, Ke.,Hu, Huifang.,Lu, Yumeng.,Zhang, Hui.,...&Shi, Jumei.(2023).Berberine derivative DCZ0358 induce oxidative damage by ROS-mediated JNK signaling in DLBCL cells.INTERNATIONAL IMMUNOPHARMACOLOGY,125,15.
MLA Feng, Qilin,et al."Berberine derivative DCZ0358 induce oxidative damage by ROS-mediated JNK signaling in DLBCL cells".INTERNATIONAL IMMUNOPHARMACOLOGY 125(2023):15.

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来源：上海药物研究所

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