A novel phosphoramide compound, DCZ0805, shows potent anti-myeloma activity via the NF-κB pathway
Abstract Background Multiple myeloma (MM) is a highly aggressive and incurable clonal plasma cell disease with a high rate of recurrence. Thus, the development of new therapies is urgently needed. DCZ0805, a novel compound synthesized from osalmide and pterostilbene, has few observed side effects. I...
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BMC
2021-05-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-021-01973-1 |
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doaj-4b71a7dc3a5d4a5f94175f8d096e0a1b2021-06-06T11:23:41ZengBMCCancer Cell International1475-28672021-05-0121111010.1186/s12935-021-01973-1A novel phosphoramide compound, DCZ0805, shows potent anti-myeloma activity via the NF-κB pathwayXuejie Gao0Bo Li1Anqi Ye2Houcai Wang3Yongsheng Xie4Dandan Yu5Zhijian Xu6Bingqing Shi7Hui Zhang8Qilin Feng9Ke Hu10Yong Zhang11Cheng Huang12Guang Yang13Jumei Shi14Weiliang Zhu15Department of Hematology, Shanghai Tenth People’s Hospital, Tongji University School of MedicineCAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of SciencesShanghai Children’s Medical Center, Shanghai JiaoTong University School of MedicineDepartment of Hematology, Shanghai Tenth People’s Hospital, Tongji University School of MedicineDepartment of Hematology, Shanghai Tenth People’s Hospital, Tongji University School of MedicineDepartment of Hematology, Shanghai Tenth People’s Hospital, Tongji University School of MedicineCAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of SciencesDepartment of Hematology, Shanghai Tenth People’s Hospital, Tongji University School of MedicineDepartment of Hematology, Shanghai Tenth People’s Hospital, Tongji University School of MedicineDepartment of Hematology, Shanghai Tenth People’s Hospital, Tongji University School of MedicineDepartment of Hematology, Shanghai Tenth People’s Hospital, Tongji University School of MedicineCAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of SciencesDepartment of Hematology, Shanghai Tenth People’s Hospital, Tongji University School of MedicineDepartment of Hematology, Shanghai Tenth People’s Hospital, Tongji University School of MedicineDepartment of Hematology, Shanghai Tenth People’s Hospital, Tongji University School of MedicineCAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of SciencesAbstract Background Multiple myeloma (MM) is a highly aggressive and incurable clonal plasma cell disease with a high rate of recurrence. Thus, the development of new therapies is urgently needed. DCZ0805, a novel compound synthesized from osalmide and pterostilbene, has few observed side effects. In the current study, we intend to investigate the therapeutic effects of DCZ0805 in MM cells and elucidate the molecular mechanism underlying its anti-myeloma activity. Methods We used the Cell Counting Kit-8 assay, immunofluorescence staining, cell cycle assessment, apoptosis assay, western blot analysis, dual-luciferase reporter assay and a tumor xenograft mouse model to investigate the effect of DCZ0805 treatment both in vivo and in vitro. Results The results showed that DCZ0805 treatment arrested the cell at the G0/G1 phase and suppressed MM cells survival by inducing apoptosis via extrinsic and intrinsic pathways. DCZ0805 suppressed the NF-κB signaling pathway activation, which may have contributed to the inhibition of cell proliferation. DCZ0805 treatment remarkably reduced the tumor burden in the immunocompromised xenograft mouse model, with no obvious toxicity observed. Conclusion The findings of this study indicate that DCZ0805 can serve as a novel therapeutic agent for the treatment of MM.https://doi.org/10.1186/s12935-021-01973-1Multiple myelomaAnti-tumor activityNF-κB |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Xuejie Gao Bo Li Anqi Ye Houcai Wang Yongsheng Xie Dandan Yu Zhijian Xu Bingqing Shi Hui Zhang Qilin Feng Ke Hu Yong Zhang Cheng Huang Guang Yang Jumei Shi Weiliang Zhu |
| spellingShingle |
Xuejie Gao Bo Li Anqi Ye Houcai Wang Yongsheng Xie Dandan Yu Zhijian Xu Bingqing Shi Hui Zhang Qilin Feng Ke Hu Yong Zhang Cheng Huang Guang Yang Jumei Shi Weiliang Zhu A novel phosphoramide compound, DCZ0805, shows potent anti-myeloma activity via the NF-κB pathway Cancer Cell International Multiple myeloma Anti-tumor activity NF-κB |
| author_facet |
Xuejie Gao Bo Li Anqi Ye Houcai Wang Yongsheng Xie Dandan Yu Zhijian Xu Bingqing Shi Hui Zhang Qilin Feng Ke Hu Yong Zhang Cheng Huang Guang Yang Jumei Shi Weiliang Zhu |
| author_sort |
Xuejie Gao |
| title |
A novel phosphoramide compound, DCZ0805, shows potent anti-myeloma activity via the NF-κB pathway |
| title_short |
A novel phosphoramide compound, DCZ0805, shows potent anti-myeloma activity via the NF-κB pathway |
| title_full |
A novel phosphoramide compound, DCZ0805, shows potent anti-myeloma activity via the NF-κB pathway |
| title_fullStr |
A novel phosphoramide compound, DCZ0805, shows potent anti-myeloma activity via the NF-κB pathway |
| title_full_unstemmed |
A novel phosphoramide compound, DCZ0805, shows potent anti-myeloma activity via the NF-κB pathway |
| title_sort |
novel phosphoramide compound, dcz0805, shows potent anti-myeloma activity via the nf-κb pathway |
| publisher |
BMC |
| series |
Cancer Cell International |
| issn |
1475-2867 |
| publishDate |
2021-05-01 |
| description |
Abstract Background Multiple myeloma (MM) is a highly aggressive and incurable clonal plasma cell disease with a high rate of recurrence. Thus, the development of new therapies is urgently needed. DCZ0805, a novel compound synthesized from osalmide and pterostilbene, has few observed side effects. In the current study, we intend to investigate the therapeutic effects of DCZ0805 in MM cells and elucidate the molecular mechanism underlying its anti-myeloma activity. Methods We used the Cell Counting Kit-8 assay, immunofluorescence staining, cell cycle assessment, apoptosis assay, western blot analysis, dual-luciferase reporter assay and a tumor xenograft mouse model to investigate the effect of DCZ0805 treatment both in vivo and in vitro. Results The results showed that DCZ0805 treatment arrested the cell at the G0/G1 phase and suppressed MM cells survival by inducing apoptosis via extrinsic and intrinsic pathways. DCZ0805 suppressed the NF-κB signaling pathway activation, which may have contributed to the inhibition of cell proliferation. DCZ0805 treatment remarkably reduced the tumor burden in the immunocompromised xenograft mouse model, with no obvious toxicity observed. Conclusion The findings of this study indicate that DCZ0805 can serve as a novel therapeutic agent for the treatment of MM. |
| topic |
Multiple myeloma Anti-tumor activity NF-κB |
| url |
https://doi.org/10.1186/s12935-021-01973-1 |
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