Chidamide, a histone deacetylase inhibitor, induces growth arrest and apoptosis in multiple myeloma cells in a caspase‑dependent manner

Yuan, Xianggui; Huang, Yurong; Teng, Yuee; Jiang, Hongyi; Xu, Yang; Zhao, Xiaoying

doi:10.3892/ol.2019.10301

Cited by 28 publications

(40 citation statements)

References 45 publications

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“…This data provides evidence of HDACi capability of restoring acetylation levels in an in vitro model of RSTS, strongly pointing to tailored future perspective in accordance with the idea of personalized medicine. We also evaluated the cytotoxicity of selected concentrations, given that HDACi are also used in oncological trials for their ability to induce selected and dose-dependent apoptosis (De Schutter and Nuyts, 2009;Yuan et al, 2019). Importantly, we did not observe neither an increase in cell death nor a decrease in cell proliferation, indicating that HDACi can boost acetylation at sub-toxic concentration in our in vitro modelling system.…”

Section: Discussionmentioning

confidence: 91%

Exogenous and endogenous HDAC inhibitor effects in Rubinstein-Taybi syndrome models

Fede

Ottaviano

Grazioli

et al. 2020

Preprint

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Rubinstein-Taybi syndrome (RSTS) is an autosomal dominant disorder with specific clinical signs and neurodevelopmental impairment. The two known proteins altered in the majority of RSTS patients are the histone acetylation regulators CBP and p300. For assessing possible ameliorative effects of exogenous and endogenous HDAC inhibitors (HDACi), we exploited in vivo and in vitro RSTS models.First, HDACi effects were tested on Drosophila melanogaster, showing molecular rescue. In the same model, we observed a shift in gut microbiota composition. We then studied HDACi effects in RSTS cell lines compared to healthy donor cells. We observed patients-specific molecular rescue of acetylation defects at subtoxic concentrations. Finally, we assessed commensal gut microbiota composition in a cohort of RSTS patients compared to healthy siblings. Intriguingly, we observed a significant depletion in butyrate-producing bacteria in RSTS patients. In conclusion, this study reports the possibility of modulating acetylation equilibrium by HDACi treatments and the importance of microbiota composition in a chromatinopathy.

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Section: Discussionmentioning

confidence: 91%

Exogenous and endogenous HDAC inhibitor effects in Rubinstein-Taybi syndrome models

Fede

Ottaviano

Grazioli

et al. 2020

Preprint

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“…HDACi are tested in oncology trials for their ability to stop tumor cell proliferation by inducing selected and dose-dependent apoptosis [ 34 ]. Thus, our observation that selected HDACi dosing does not modulate cell proliferation or death in RSTS cells indicates that HDACi can boost acetylation at a sub-toxic concentration, at least in vitro.…”

Section: Discussionmentioning

confidence: 99%

Insights into the Role of the Microbiota and of Short-Chain Fatty Acids in Rubinstein–Taybi Syndrome

Fede

Ottaviano

Grazioli

et al. 2021

IJMS

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The short-chain fatty acid butyrate, produced by the gut microbiota, acts as a potent histone deacetylase (HDAC) inhibitor. We assessed possible ameliorative effects of butyrate, relative to other HDAC inhibitors, in in vitro and in vivo models of Rubinstein–Taybi syndrome (RSTS), a severe neurodevelopmental disorder caused by variants in the genes encoding the histone acetyltransferases CBP and p300. In RSTS cell lines, butyrate led to the patient-specific rescue of acetylation defects at subtoxic concentrations. Remarkably, we observed that the commensal gut microbiota composition in a cohort of RSTS patients is significantly depleted in butyrate-producing bacteria compared to healthy siblings. We demonstrate that the effects of butyrate and the differences in microbiota composition are conserved in a Drosophila melanogaster mutant for CBP, enabling future dissection of the gut–host interactions in an in vivo RSTS model. This study sheds light on microbiota composition in a chromatinopathy, paving the way for novel therapeutic interventions.

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“…Many studies have shown that chidamide has anti-tumor effects in a variety of hematological malignancies (such as lymphoma, myeloma, and leukemia)[ 22 ]. Many studies have confirmed the anti-myeloma effect of chidamide, and it mainly promotes the G0/G1 arrest and apoptosis of G0/G1 in a caspase-dependent manner in myeloma cells[ 23 ]. We herein reported the results of a highly successful treatment for the diagnosis of pPCL 5 years ago.…”

Section: Discussionmentioning

confidence: 99%

Venetoclax in combination with chidamide and dexamethasone in relapsed/refractory primary plasma cell leukemia without t(11;14): A case report

Yang¹,

Fu²,

Chen³

et al. 2021

WJCC

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BACKGROUND Conventional therapies for primary plasma cell leukemia (pPCL) are usually ineffective, with a short remission time with the use of multiple myeloma medications, showing aggressiveness of pPCL. B-cell lymphoma-2 inhibitor venetoclax is usually used for relapsed/refractory multiple myeloma (RRMM) with t(11;14). There are very few studies published on the use of venetoclax in pPCL without t(11;14). Similarly, histone deacetylase inhibitors are considered effective for the treatment of RRMM, but there are no reports on their use in pPCL. CASE SUMMARY A 57-year-old woman with severe anemia, thrombocytopenia, multiple bone destruction, impaired renal function, and 42.7% of peripheral plasma cells is reported. After multiple chemotherapy regimens and chimeric antigen receptor T-cell treatment, the disease progressed again. The patient had very good partial response and was maintained for a long time on venetoclax in combination with chidamide and dexamethasone therapy. CONCLUSION The success of venetoclax-chidamide-dexamethasone combination therapy in achieving a very good partial response suggested that it can be used for refractory/relapsed pPCL patients who have been exhausted with the use of various drug combinations and had poor survival outcomes.

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Chidamide, a histone deacetylase inhibitor, induces growth arrest and apoptosis in multiple myeloma cells in a caspase‑dependent manner

Cited by 28 publications

References 45 publications

Exogenous and endogenous HDAC inhibitor effects in Rubinstein-Taybi syndrome models

Exogenous and endogenous HDAC inhibitor effects in Rubinstein-Taybi syndrome models

Insights into the Role of the Microbiota and of Short-Chain Fatty Acids in Rubinstein–Taybi Syndrome

Venetoclax in combination with chidamide and dexamethasone in relapsed/refractory primary plasma cell leukemia without t(11;14): A case report

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