A novel alkaloid compound, DCZ0358, exerts significant antitumor activity in bortezomib-resistant multiple myeloma cells through inhibition of JAK2/STAT3 pathway

Zhang Bibo; Li Bo; Xie Yongsheng; Chang Shuaikang; Xu Zhijian; Hu Huifang; Chen Gege; Zhang Ting; He Jun; Wu Xiaosong; Zhu Huabin; Lai Weiming; Song Dongliang; Lu Ying; Jia Xinyan; Zhu Weiliang; Shi Jumei

doi:10.3724/abbs.2023014

Acta Biochimica et Biophysica Sinica (Feb 2023)

A novel alkaloid compound, DCZ0358, exerts significant antitumor activity in bortezomib-resistant multiple myeloma cells through inhibition of JAK2/STAT3 pathway

Zhang Bibo,
Li Bo,
Xie Yongsheng,
Chang Shuaikang,
Xu Zhijian,
Hu Huifang,
Chen Gege,
Zhang Ting,
He Jun,
Wu Xiaosong,
Zhu Huabin,
Lai Weiming,
Song Dongliang,
Lu Ying,
Jia Xinyan,
Zhu Weiliang,
Shi Jumei

Affiliations

Zhang Bibo: ["Department of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China","Department of Hematology, The Affiliated People’s Hospital of Ningbo University, Ningbo 315000, China"]
Li Bo: ["CAS Key Laboratory of Receptor Research, Stake Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"]
Xie Yongsheng: ["Department of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China"]
Chang Shuaikang: ["Department of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China"]
Xu Zhijian: ["CAS Key Laboratory of Receptor Research, Stake Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"]
Hu Huifang: ["CAS Key Laboratory of Receptor Research, Stake Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"]
Chen Gege: ["Department of Hematology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China"]
Zhang Ting: ["Department of Hematology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China"]
He Jun: ["Department of Hematology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China"]
Wu Xiaosong: ["Department of Hematology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China"]
Zhu Huabin: ["Department of Hematology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China"]
Lai Weiming: ["Department of Hematology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China"]
Song Dongliang: ["Department of Hematology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China"]
Lu Ying: ["Department of Hematology, The Affiliated People’s Hospital of Ningbo University, Ningbo 315000, China"]
Jia Xinyan: ["Department of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China"]
Zhu Weiliang: ["CAS Key Laboratory of Receptor Research, Stake Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"]
Shi Jumei: ["Department of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China"]

DOI: https://doi.org/10.3724/abbs.2023014
Journal volume & issue: Vol. 55
pp. 215 – 224

Abstract

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Multiple myeloma (MM), the seco nd most common haematological malignancy, is currently incurable because patients often develop multiple drug resistance and experience subsequent relapse of the disease. This study aims to identify a potential therapeutic agent that can counter bortezomib (BTZ) resistance in MM. DCZ0358, a novel alkaloid compound, is found to exert potent cytotoxic effects against BTZ-resistant MM cells in vivo and in vitro. The anti-myeloma activity of DCZ0358 is associated with inhibition of cell proliferation, promotion of cell apoptosis via caspase-mediated apoptotic pathways, and induction of G0/G1 phase arrest via downregulation of cyclin D1, CDK4, and CDK6. Further investigation of the molecular mechanism shows that DCZ0358 suppresses the JAK2/STAT3 signaling pathway. In conclusion, DCZ0358 can successfully counter BTZ resistance in MM cells. This study provides evidence that warrants future preclinical assessments of DCZ0358 as a therapeutic agent against BTZ resistance in MM.

Published in Acta Biochimica et Biophysica Sinica

ISSN: 1672-9145 (Print); 1745-7270 (Online)
Publisher: China Science Publishing & Media Ltd.
Country of publisher: China
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry; Science: Biology (General): Genetics
Website: https://www.sciengine.com/ABBS/home

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