A novel alkaloid compound, DCZ0358, exerts significant antitumor activity in bortezomib-resistant multiple myeloma cells through inhibition of JAK2/STAT3 pathway
Multiple myeloma (MM), the seco <styleredit/>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...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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China Science Publishing & Media Ltd.
2023-02-01
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| Series: | Acta Biochimica et Biophysica Sinica |
| Subjects: | |
| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2023014 |
| _version_ | 1827769558175318016 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Zhang Bibo |
| collection | DOAJ |
| description | Multiple myeloma (MM), the seco <styleredit/>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. |
| first_indexed | 2024-03-11T12:25:57Z |
| format | Article |
| id | doaj.art-abcf3cedb3ee4a849ce5182cd767f0fb |
| institution | Directory Open Access Journal |
| issn | 1672-9145 |
| language | English |
| last_indexed | 2024-03-11T12:25:57Z |
| publishDate | 2023-02-01 |
| publisher | China Science Publishing & Media Ltd. |
| record_format | Article |
| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj.art-abcf3cedb3ee4a849ce5182cd767f0fb2023-11-06T08:59:24ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452023-02-015521522410.3724/abbs.202301420d259ccA novel alkaloid compound, DCZ0358, exerts significant antitumor activity in bortezomib-resistant multiple myeloma cells through inhibition of JAK2/STAT3 pathwayZhang Bibo0Li Bo1Xie Yongsheng2Chang Shuaikang3Xu Zhijian4Hu Huifang5Chen Gege6Zhang Ting7He Jun8Wu Xiaosong9Zhu Huabin10Lai Weiming11Song Dongliang12Lu Ying13Jia Xinyan14Zhu Weiliang15Shi Jumei16["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"]["CAS Key Laboratory of Receptor Research, Stake Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"]["Department of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China"]["Department of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China"]["CAS Key Laboratory of Receptor Research, Stake Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"]["CAS Key Laboratory of Receptor Research, Stake Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"]["Department of Hematology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China"]["Department of Hematology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China"]["Department of Hematology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China"]["Department of Hematology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China"]["Department of Hematology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China"]["Department of Hematology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China"]["Department of Hematology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China"]["Department of Hematology, The Affiliated People’s Hospital of Ningbo University, Ningbo 315000, China"]["Department of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China"]["CAS Key Laboratory of Receptor Research, Stake Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"]["Department of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China"]Multiple myeloma (MM), the seco <styleredit/>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. https://www.sciengine.com/doi/10.3724/abbs.2023014DCZ0358apoptosiscell cycle arrestmultiple myelomaJAK2/STAT3 pathway |
| spellingShingle | 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 A novel alkaloid compound, DCZ0358, exerts significant antitumor activity in bortezomib-resistant multiple myeloma cells through inhibition of JAK2/STAT3 pathway Acta Biochimica et Biophysica Sinica DCZ0358 apoptosis cell cycle arrest multiple myeloma JAK2/STAT3 pathway |
| title | A novel alkaloid compound, DCZ0358, exerts significant antitumor activity in bortezomib-resistant multiple myeloma cells through inhibition of JAK2/STAT3 pathway |
| title_full | A novel alkaloid compound, DCZ0358, exerts significant antitumor activity in bortezomib-resistant multiple myeloma cells through inhibition of JAK2/STAT3 pathway |
| title_fullStr | A novel alkaloid compound, DCZ0358, exerts significant antitumor activity in bortezomib-resistant multiple myeloma cells through inhibition of JAK2/STAT3 pathway |
| title_full_unstemmed | A novel alkaloid compound, DCZ0358, exerts significant antitumor activity in bortezomib-resistant multiple myeloma cells through inhibition of JAK2/STAT3 pathway |
| title_short | A novel alkaloid compound, DCZ0358, exerts significant antitumor activity in bortezomib-resistant multiple myeloma cells through inhibition of JAK2/STAT3 pathway |
| title_sort | novel alkaloid compound dcz0358 exerts significant antitumor activity in bortezomib resistant multiple myeloma cells through inhibition of jak2 stat3 pathway |
| topic | DCZ0358 apoptosis cell cycle arrest multiple myeloma JAK2/STAT3 pathway |
| url | https://www.sciengine.com/doi/10.3724/abbs.2023014 |
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