The short-term effect of histone deacetylase�inhibitors, chidamide and valproic acid, on�the�NF‑κB�pathway in multiple myeloma cells

Liu, Zhaoyun; Qian, Ji; Wang, Yangyang; Li, Yanqi; M, Fu; Xiang, Chenhuan; Fu, Rong

doi:10.3892/ijmm.2018.3963

Cited by 6 publications

(8 citation statements)

References 41 publications

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“…Thus, it is urgent demand to develop novel drugs against MM. CHI, a novel orally HDACi has been approved by the CFDA for the treatment of PTCL 14 , was found to be potential therapeutic agent in MM in vitro and in vivo 15 , 17 , 27 . In the present study, we showed for the first time that combination of CHI and BTZ significantly increased cell death compared with CHI or BTZ alone.…”

Section: Discussionmentioning

confidence: 99%

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Chidamide, a subtype-selective histone deacetylase inhibitor, enhances Bortezomib effects in multiple myeloma therapy

He¹,

Jiang²,

Zhang³

et al. 2021

J. Cancer

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Drug resistance is the major cause for disease relapse and patient death in multiple myeloma (MM). It is an urgent need to develop new therapies to overcome drug resistance in MM. Chidamide (CHI), a novel oral HDAC inhibitor targeting HDAC1, 2, 3 and 10, has shown potential therapeutic effect in MM. In this study, we determined that CHI exhibited significant anti-tumor effect on MM cells both in vitro and in vivo, which was positively correlated with the expression of HDAC1. Meanwhile, CHI enhanced Bortezomib (BTZ) effects synergistically in MM cells and a combination of CHI with BTZ induced myeloma cell apoptosis and G0/G1 arrest in vitro and in vivo. Mechanistically, the synergistic anti-tumor effect of CHI and BTZ was related with the increased production of reactive oxygen species (ROS) dependent DNA damage and the changes of cell apoptosis and cycle pathways. Our data indicate that CHI may be a suitable drug to sensitize BTZ in MM cells, which provides novel insight into the therapy for MM patients.

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Section: Discussionmentioning

confidence: 99%

“…As an epigenetic modulator, CHI induced tumor cell growth arrest and apoptosis and enhanced cellular antitumor immunity [12][13][14]. CHI exhibited significant cytotoxicity against MM cells co-cultured with bone mesenchymal stromal cells and CHI-pretreated osteoclasts in recent studies [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Chidamide, a subtype-selective histone deacetylase inhibitor, enhances Bortezomib effects in multiple myeloma therapy

He¹,

Jiang²,

Zhang³

et al. 2021

J. Cancer

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“…HDAC-inhibiting and anti-myeloma activities of chidamide have been demonstrated in MM. 25,[28][29][30] It has been reported that HDAC inhibitor vorinostat increased the levels of ROS in drug-resistant cells, which caused selective apoptotic death of only the drug-resistant tumour cells. 15 Thus, we speculated that the overproduction of ROS may be responsible for the anti-myeloma activity of chidamide.…”

Section: Discussionmentioning

confidence: 99%

Chidamide-Induced Accumulation of Reactive Oxygen Species Increases Lenalidomide Sensitivity Against Multiple Myeloma Cells

Jiang¹,

Zhang²,

Zhu³

et al. 2021

OTT

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Background: Lenalidomide, an immunomodulatory drug (IMiD), is an effective therapy for the treatment of multiple myeloma (MM). However, prolonged treatment may be accompanied by toxicity, second primary malignancies, and drug resistance. There is an inherent vulnerability in MM cells that high rates of immunoglobulin synthesis resulting in the high level of reactive oxygen species (ROS). This provides a therapeutic potential for MM. Materials and Methods: The intracellular ROS levels, H 2 O 2 production and glutathione (GSH) levels were measured using detection kit. Cell viability was evaluated using cell-counting kit-8 (CCK-8) and soft agar colony formation assay. Apoptosis was determined in whole living cells using flow cytometry. Chidamide and its anti-myeloma efficacy in combination with lenalidomide were characterized in MM cell lines in vitro and in a mouse xenograft model. Moreover, Western blotting, immunofluorescence and immunohistochemical studies were performed. Results: ROS levels increased in a time-and dose-dependent manner with chidamide treatment. Moreover, the GSH levels were decreased and the mRNA level of SLC7A11 downregulated after chidamide treatment. The co-treatment with chidamide and lenalidomide increased apoptosis and proliferation inhibition, with combination index (CI) in the synergistic range (0.2-0.5) using the Chou-Talalay method. The cooperative anti-myeloma efficacy was confirmed in the murine model, and immunohistochemical studies also supported this potentiation. Chidamide enhanced the effect of lenalidomide-induced degradation of IKZF1 and IKZF3 by elevating H 2 O 2 . In addition, co-treatment with chidamide and lenalidomide increased biomarkers of caspase and DNA damage. Conclusion: Elevated ROS production may constitute a potential biochemical basis for antimyeloma effects of chidamide plus lenalidomide. The results of this study confirm the synergistic effect of chidamide and lenalidomide against MM and provide a promising therapeutic strategy for MM.

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“…Chidamide also inhibits pancreatic cancer cell proliferation and induces mitochondrial apoptosis by modulating bax/bcl-2 family proteins levels (Zhao and He, 2015). By blocking NF-kB signaling pathway, Chidamide can inhibit cell proliferation and enhance drug sensitivity in multiple myeloma (Liu et al, 2019). Chidamide inhibits MDS and AML cells viability via JAK2/STAT3 signaling (Zhao et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Chidamide Inhibits Acute Myeloid Leukemia Cell Proliferation by lncRNA VPS9D1-AS1 Downregulation via MEK/ERK Signaling Pathway

Lin

Que

et al. 2020

Front. Pharmacol.

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Irregular histone modification and aberrant lncRNAs expression are closely related to the occurrence of tumors including acute myeloid leukemia (AML). However, the effects and specific underlying molecular mechanism of histone deacetylase inhibitors on lncRNA expression in AML cells are unclear. Here, we reported the effects of a novel histone deacetylase inhibitor Chidamide on proliferation and lncRNA expression in AML cells. Chidamide inhibited cell proliferation, blocked G1/S phase transition, and induced cell apoptosis through the caspase-dependent apoptotic pathway in AML cells. Chidamide also inhibited the formation of subcutaneous tumors. Transcriptome sequencing results showed that 1,195 lncRNAs were co-upregulated and 780 lncRNAs were codownregulated after Chidamide treatment of SKM-1 cells and THP-1 cells. Combined with transcriptome sequencing data and the gene expression profiling interactive analysis dataset, we found that VPS9D1-AS1 expression was negatively correlated with the survival of AML patients. VPS9D1-AS1 knockdown inhibited cell proliferation, arrested cell cycle, as well as inhibited the formation of subcutaneous tumors in vivo. VPS9D1-AS1 overexpression had the reverse effect. Furthermore, VPS9D1-AS1 knockdown inhibited the MEK/ERK signaling pathway, and thus enhanced the inhibitory effect of Chidamide on AML cell proliferation. These findings suggested that targeted regulation of VPS9D1-AS1 might overcome the limitations of Chidamide in the treatment of AML.

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The short-term effect of histone deacetylase�inhibitors, chidamide and valproic acid, on�the�NF‑κB�pathway in multiple myeloma cells

Cited by 6 publications

References 41 publications

Chidamide, a subtype-selective histone deacetylase inhibitor, enhances Bortezomib effects in multiple myeloma therapy

Chidamide, a subtype-selective histone deacetylase inhibitor, enhances Bortezomib effects in multiple myeloma therapy

Chidamide-Induced Accumulation of Reactive Oxygen Species Increases Lenalidomide Sensitivity Against Multiple Myeloma Cells

Chidamide Inhibits Acute Myeloid Leukemia Cell Proliferation by lncRNA VPS9D1-AS1 Downregulation via MEK/ERK Signaling Pathway

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