Lycorine targets multiple myeloma stem cell-like cells by inhibition of Wnt/β-catenin pathway
Haiqin Wang
Molecular Biology Research Center & Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China
These authors contributed equally.Search for more papers by this authorYanfei Gong
Molecular Biology Research Center & Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China
These authors contributed equally.Search for more papers by this authorLong Liang
Molecular Biology Research Center & Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China
Hematology Department, Xiangya Hospital, Central South University, Changsha, China
Search for more papers by this authorLing Xiao
Department of Histology and Embryology of School of Basic Medical Sciences, Central South University, Changsha, China
Search for more papers by this authorHui Yi
Molecular Biology Research Center & Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China
Search for more papers by this authorMao Ye
Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Hunan University, Changsha, China
Search for more papers by this authorMridul Roy
Molecular Biology Research Center & Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China
Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Hunan University, Changsha, China
Search for more papers by this authorJiliang Xia
Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, China
Search for more papers by this authorWen Zhou
Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, China
Search for more papers by this authorChaoying Yang
Molecular Biology Research Center & Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China
Search for more papers by this authorXiaokai Shen
Xiangya Medical School, Central South University, Changsha, China
Search for more papers by this authorBoxin Zhang
Xiangya Medical School, Central South University, Changsha, China
Search for more papers by this authorZhenzhen Li
Molecular Biology Research Center & Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China
Search for more papers by this authorCorresponding Author
Jing Liu
Molecular Biology Research Center & Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China
Correspondence: Xiaojuan Xiao and Jing Liu, Molecular Biology Research Center & Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China.
E-mails: [email protected]; [email protected]
Hui Zhou, Lymphoma & Hematology Department, the Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, China.
E-mail: [email protected]
Search for more papers by this authorCorresponding Author
Hui Zhou
Lymphoma & Hematology Department, the Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, China
Correspondence: Xiaojuan Xiao and Jing Liu, Molecular Biology Research Center & Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China.
E-mails: [email protected]; [email protected]
Hui Zhou, Lymphoma & Hematology Department, the Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, China.
E-mail: [email protected]
Search for more papers by this authorCorresponding Author
Xiaojuan Xiao
Molecular Biology Research Center & Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China
Correspondence: Xiaojuan Xiao and Jing Liu, Molecular Biology Research Center & Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China.
E-mails: [email protected]; [email protected]
Hui Zhou, Lymphoma & Hematology Department, the Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, China.
E-mail: [email protected]
Search for more papers by this authorHaiqin Wang
Molecular Biology Research Center & Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China
These authors contributed equally.Search for more papers by this authorYanfei Gong
Molecular Biology Research Center & Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China
These authors contributed equally.Search for more papers by this authorLong Liang
Molecular Biology Research Center & Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China
Hematology Department, Xiangya Hospital, Central South University, Changsha, China
Search for more papers by this authorLing Xiao
Department of Histology and Embryology of School of Basic Medical Sciences, Central South University, Changsha, China
Search for more papers by this authorHui Yi
Molecular Biology Research Center & Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China
Search for more papers by this authorMao Ye
Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Hunan University, Changsha, China
Search for more papers by this authorMridul Roy
Molecular Biology Research Center & Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China
Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Hunan University, Changsha, China
Search for more papers by this authorJiliang Xia
Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, China
Search for more papers by this authorWen Zhou
Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, China
Search for more papers by this authorChaoying Yang
Molecular Biology Research Center & Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China
Search for more papers by this authorXiaokai Shen
Xiangya Medical School, Central South University, Changsha, China
Search for more papers by this authorBoxin Zhang
Xiangya Medical School, Central South University, Changsha, China
Search for more papers by this authorZhenzhen Li
Molecular Biology Research Center & Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China
Search for more papers by this authorCorresponding Author
Jing Liu
Molecular Biology Research Center & Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China
Correspondence: Xiaojuan Xiao and Jing Liu, Molecular Biology Research Center & Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China.
E-mails: [email protected]; [email protected]
Hui Zhou, Lymphoma & Hematology Department, the Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, China.
E-mail: [email protected]
Search for more papers by this authorCorresponding Author
Hui Zhou
Lymphoma & Hematology Department, the Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, China
Correspondence: Xiaojuan Xiao and Jing Liu, Molecular Biology Research Center & Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China.
E-mails: [email protected]; [email protected]
Hui Zhou, Lymphoma & Hematology Department, the Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, China.
E-mail: [email protected]
Search for more papers by this authorCorresponding Author
Xiaojuan Xiao
Molecular Biology Research Center & Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China
Correspondence: Xiaojuan Xiao and Jing Liu, Molecular Biology Research Center & Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, China.
E-mails: [email protected]; [email protected]
Hui Zhou, Lymphoma & Hematology Department, the Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, China.
E-mail: [email protected]
Search for more papers by this authorSummary
Multiple myeloma (MM) is characterised by the proliferation and accumulation of malignant plasma cells in the bone marrow. Despite the progress in treatment over the last few years, MM remains incurable and the majority of patients relapse. MM stem-like cells (MMSCs) have been considered as the main reason for drug resistance and eventual relapse. Currently, therapeutic agents are not enough to eradicate MMSCs, and finding effective strategies to eradicate MMSCs may improve the outcome of patients. Here we showed that lycorine, a natural compound from the Amaryllidaceae species, effectively inhibits the proliferation of myeloma cells from cell lines or patients, mainly through decreasing ALDH1+ cells. Mechanistically, lycorine decreases the MMSC population through inhibition of the Wnt/β-catenin pathway by reducing the β-catenin protein level. Moreover, lycorine could overcome the increasing proportion of ALDH1+ cells caused by bortezomib (BTZ) treatment, and a combination BTZ and lycorine have a synergistic effect on anti-myeloma cells. Furthermore, we found a similar reduction of MMSC characteristics by lycorine in BTZ-resistant MM cells and primary CD138+ plasma cells. Collectively, our findings indicate lycorine as a promising agent to target MMSCs to overcome the drug resistance of BTZ, and that, alone or in combination with BTZ, lycorine is a potential therapeutic strategy for MM treatments.
Conflict of interests
The authors declare no conflict of interests.
Supporting Information
| Filename | Description |
|---|---|
| bjh16477-sup-0001-Supinfo.docWord document, 1,010 KB |
Fig S1. Analysis of the expression of ALDH1A1 and ABCG2 in ARP1 and KMS11 cells treated with different concentrations of lycorine by western blot. Loading control: α-tubulin or GAPDH. Fig S2. After different concentrations of lycorine treatment, SP and MP cells viability examined using the CCK-8 assay. Error bars represent SD values determined by triplicate measurements. ns: P＞0.05. Fig S3. Analysis of ARP1 ALDH1+ and ALDH1- cells using the standard apoptotic assay, and the right shifted peak demonstrates cells undergoing apoptosis. Fig S4. Analysis of the expression of LC3B in ALDH1+ and ALDH1- cells treated with different concentrations of lycorine by western blot. Loading control: α-tubulin. Fig S5. After different concentrations of lycorine treatment, BMSCs cell viability was examined using the CCK-8 assay. Error bars represent SD values determined by triplicate measurements. ns: P＞0.05. Fig S6. After different concentrations of lycorine treatment, ANBL6 and ANBL6-BR cell viability was examined using the CCK-8 assay. Error bars represent SD values determined by triplicate measurements. **P＜0.01 Fig S7. ABCG2 protein expression in ANBL6 and ANBL6-BR cells. Loading control: α-tubulin. Fig S8. Analysis of the expression of β-catenin, C-MYC, CCND1 in ANBL6 and ANBL6-BR cells treated with different concentrations of lycorine by western blot. Loading control: α-tubulin. Table S1. qRT-PCR primers |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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