Therapeutic effects of the novel subtype-selective histone deacetylase inhibitor chidamide on myeloma-associated bone disease

He, Jingsong; Chen, Qingxiao; Gu, Huiyao; Chen, Jing; Zhang, Enfan; Guo, Xing; Huang, Xi; Yan, Haimeng; He, Donghua; Yang, Yang; Zhao, Yi; Wang, Gang; Huang, He; Yi, Qing; Zhang, Cai

doi:10.3324/haematol.2017.181172

Cited by 23 publications

(29 citation statements)

References 34 publications

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“…Thus, tumor cells are surrounded by a large number of cells able to synthesize estrogens which promote malignant cell growth. In addition, the dynamic changes that take place within tumor microenvironment sometimes enable malignant cells to develop resistance to chemotherapeutic drugs or to radiation, because they induce a sublethal exposition of tumor cells to the different treatments [19]. Melatonin, within its antitumor actions, counteracts the effects of estrogens through different actions by interacting at different levels with estrogen signaling pathways [7,8,9,20,21,22].…”

Section: Discussionmentioning

confidence: 99%

Melatonin Modulation of Radiation and Chemotherapeutics-induced Changes on Differentiation of Breast Fibroblasts

González-González

Nieto

González

et al. 2019

IJMS

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Melatonin exerts oncostatic actions and sensitizes tumor cells to chemotherapeutics or radiation. In our study, we investigated the effects of docetaxel, vinorelbine, and radiation on human breast fibroblasts and its modulation by melatonin. Docetaxel or vinorelbine inhibits proliferation and stimulates the differentiation of breast preadipocytes, by increasing C/EBPα and PPARγ expression and by downregulating tumor necrosis factor α (TNFα), interleukin 6 (IL-6), and IL-11 expression. Radiation inhibits both proliferation and differentiation through the downregulation of C/EBPα and PPARγ and by stimulating TNFα expression. In addition, docetaxel and radiation decrease aromatase activity and expression by decreasing aromatase promoter II and cyclooxygenases 1 and 2 (COX-1 and COX-2) expression. Melatonin potentiates the stimulatory effect of docetaxel and vinorelbine on differentiation and their inhibitory effects on aromatase activity and expression, by increasing the stimulatory effect on C/EBPα and PPARγ expression and the downregulation of antiadipogenic cytokines and COX expression. Melatonin also counteracts the inhibitory effect of radiation on differentiation of preadipocytes, by increasing C/EBPα and PPARγ expression and by decreasing TNFα expression. Melatonin also potentiates the inhibitory effect exerted by radiation on aromatase activity and expression by increasing the downregulation of promoter II, and COX-1 and COX-2 expression. Our findings suggest that melatonin modulates regulatory effects induced by chemotherapeutic drugs or radiation on preadipocytes, which makes it a promising adjuvant for chemotherapy and radiotherapy sensibilization.

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Section: Discussionmentioning

confidence: 99%

Melatonin Modulation of Radiation and Chemotherapeutics-induced Changes on Differentiation of Breast Fibroblasts

González-González

Nieto

González

et al. 2019

IJMS

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“…As a novel histone deacetylase inhibitor, chidamide (CDM) has been recently used for several clinical trials as a potential anti-tumor drug in China. It shows some effects on cancer inhibition in T-cell lymphoma (19, 47–49), multiple myeloma (50), and pancreatic cancer (51), although there are no reports regarding the effects of chidamide alone on NKTCL inhibition. In this study, we showed that chidamide (CDM) alone has a small effect on NKTCL tumor growth and EBV replication, while when it is used together with aspirin, it significantly potentiated aspirin-mediated tumor suppression in NKTCL cells.…”

Section: Discussionmentioning

confidence: 99%

Aspirin Inhibits Natural Killer/T-Cell Lymphoma by Modulation of VEGF Expression and Mitochondrial Function

Zhang

Jiao

et al. 2019

Front. Oncol.

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Extranodal nasal-type natural killer/T-cell lymphoma (NKTCL) is an Epstein-Barr virus (EBV)-associated lymphoma with a strong tendency relapse or be refractory in response to chemotherapy. Development of a new strategy for NKTCL treatment is still quite necessary. In this study, we found that aspirin treatment suppresses VEGF expression in NKTCL SNK-6 cells. Further investigation showed that aspirin treatment increases histone methylation in the range of −100~0 that is proximal to the transcription start site on the VEGF promoter, subsequently decreasing the binding ability of Sp1 to the VEGF promoter with VEGF suppression. Furthermore, aspirin treatment modulates mitochondrial function with increased ROS formation and apoptosis in NKTCL cells. Aspirin treatment alone slightly inhibits NKTCL SNK-6 tumor growth and EBV replication; while in the presence of histone deacetylase inhibitor (HDACi) chidamide (CDM), aspirin significantly suppresses the VEGF signaling pathway with increased ROS overgeneration and EBV inhibition. We also showed that with the addition of chidamide, aspirin significantly suppresses NKTCL tumor growth in both in vitro cell culture and in vivo mouse model with prolonged mouse survival. This is the first time that the potential mechanism for aspirin-mediated VEGF suppression and anti-tumor effect has been discovered, and this study provides a new strategy for anti-tumor drug development for NKTCL treatment based on aspirin-mediated targeting of the VEGF signaling pathway and ROS formation.

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“…As an inhibitor of histone deacetylases (HDAC), trichostatin A (TSA) has been reported for a potent inducer of tumor cell growth arrest, and apoptosis in many diverse transformed cells and tumor-bearing animals by regulating the expression of tumor suppressor genes [38]. HDAC inhibitors are gradually in use for lymphoma and multiple myeloma in this decade [39, 40]. The use of HDAC inhibitor in our EMI patients also appears a modest curative effect (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Circular RNA regulatory network reveals cell–cell crosstalk in acute myeloid leukemia extramedullary infiltration

Sun

Guo

et al. 2018

J Transl Med

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BackgroundAcute myeloid leukemia can develop as myoblasts infiltrate into organs and tissues anywhere other than the bone marrow, which called extramedullary infiltration (EMI), indicating a poor prognosis. Circular RNAs (circRNAs) are a novel class of non-coding RNAs that feature covalently closed continuous loops, suggesting their potential as micro RNA (miRNA) “sponges” that can participate in biological processes and pathogenesis. However, investigations on circRNAs in EMI were conducted rarely. In this study, the overall alterations of circRNAs and their regulatory network between EMI and non-EMI AML were delineated.MethodsCircRNA and whole genome microarrays derived from EMI and non-EMI AML bone marrow mononuclear cells were carried out. Functional analysis was performed via Gene Ontology and KEGG test methods. The speculated functional roles of circRNAs were based on mRNAs and predicted miRNAs that played intermediate roles. Integrated bioinformatic analysis was conducted to further characterize the circRNA/miRNA/mRNA regulatory network and identify the functions of distinct circRNAs. The Cancer Genome Atlas (TCGA) data were acquired to evaluate the poor prognosis of distinct target genes of circRNAs. Reverse transcription-quantitative polymerase chain reaction was conducted to identify the expression of has_circRNA_0004520. Connectivity map (CMap) analysis was further performed to predict potential therapeutic agents for EMI.Results253 circRNAs and 663 genes were upregulated and 259 circRNAs and 838 genes were downregulated in EMI compared to non-EMI AML samples. GO pathways were enriched in progress including cell adhesion (GO:0030155; GO:0007155), migration (GO:0016477; GO:0030334), signal transduction (GO:0009966; GO:0007165) and cell–cell communication. Overlapping circRNAs envolved in pathways related to regulate cell–cell crosstalk, 17 circRNAs were chosen based on their putative roles. 7 target genes of 17 circRNAs (LRRK1, PLXNB2, OLFML2A, LYPD5, APOL3, ZNF511, and ASB2) indicated a poor prognosis, while overexpression of PAPLN and NRXN3 indicated a better one based on data from TCGA. LY-294002, trichostatin A and SB-202190 were identified as therapeutic candidates for EMI by the CMap analysis.ConclusionTaken together, this study reveals the overall alterations of circRNA and mRNA involved in EMI and suggests potential circRNAs may act as biomarkers and targets for early diagnosis and treatment of EMI.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1726-x) contains supplementary material, which is available to authorized users.

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Therapeutic effects of the novel subtype-selective histone deacetylase inhibitor chidamide on myeloma-associated bone disease

Cited by 23 publications

References 34 publications

Melatonin Modulation of Radiation and Chemotherapeutics-induced Changes on Differentiation of Breast Fibroblasts

Melatonin Modulation of Radiation and Chemotherapeutics-induced Changes on Differentiation of Breast Fibroblasts

Aspirin Inhibits Natural Killer/T-Cell Lymphoma by Modulation of VEGF Expression and Mitochondrial Function

Circular RNA regulatory network reveals cell–cell crosstalk in acute myeloid leukemia extramedullary infiltration

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