Chidamide, a novel histone deacetylase inhibitor (HDACI), shows anticancer ability against leukemia and solid tumors. Decitabine (5-Aza-2'-deoxycytidine, DAC), an anti-leukemic drug, is effective in treating acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). In our study, we investigated the anti-leukemic ability of chidamide, as well as its combination with decitabine in leukemia cells (HL60 and NB4). The results showed that the inhibitive effect of chidamide was dose- and time-dependent at concentration of 0.25-8 μM. The proliferation of HL60 and NB4 cells were significantly inhibited by chidamide or its combination with decitabine. The combination had a remarkable synergistic anti-leukemic effect. Chidamide increased the levels of acetylated histone H3 in both HL60 and NB4 cells by effectively inhibiting histone deacetylases (HDAC) enzymatic activities. The cells were blocked in G/G phase by chidamide, but when chidamide was combined with decitabine, the cell cycle was mainly blocked in G/M phase, accompanied by the induction of p21 expression. In both cases (chidamide or chidamide combined with decitabine), apoptosis of tumor cells was induced through up-regulation of Bax and Caspase-3, and down-regulation of Bcl-2, showing a synergistic cytotoxicity. In conclusion, our results suggested that chidamide in combination with decitabine might be an effective therapy for AML.
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Genes (Basel)
December 2024
Department of Bioinformatics, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany.
Epigenetic dysregulation is a common feature of cancer. Promoter demethylation of tumor-promoting genes and global DNA hypomethylation may trigger tumor progression. Epigenetic changes are unstable; thus, research has focused on detecting remedies that target epigenetic regulators.
View Article and Find Full Text PDFFront Oncol
December 2024
Department of Hematology, The 923rd Hospital of the Joint Logistics Support Force of the People's Liberation Army, Nanning, China.
The management of patients with myelodysplastic syndrome (MDS) refractory to hypomethylating agents (HMAs) remains a challenge with few reliably effective treatments. Preclinical studies have shown that the inhibition of the nuclear export protein XPO1 causes nuclear accumulation of p53 and disruption of NF-κB signaling; both of which are relevant targets for MDS. Selinexor is an XPO1 inhibitor with demonstrated efficacy in MDS patients.
View Article and Find Full Text PDFFront Pharmacol
December 2024
Department of Pharmacy, Zhengzhou No. 7 People's Hospital, Zhengzhou, Henan, China.
Background: Studies have shown that DNA methylation of the CACNA1C gene is involved in the pathogenesis of various diseases and the mechanism of drug action. However, its relationship with atrial fibrillation (AF) remains largely unexplored.
Objective: To investigate the association between DNA methylation of the CACNA1C gene and AF by combining decitabine (5-Aza-2'-deoxycytidine, AZA) treatment with multi-omics analysis.
Transl Oncol
December 2024
Department of Stomatology, Children's Hospital of Chongqing Medical University, Chongqing, PR China.
The low expression of period circadian regulator 3 (PER3) in head and neck squamous cell carcinoma is closely correlated with tumor size and invasion depth. Hypoxia-inducible factor 1 subunit alpha (HIF-1α) regulates epithelial-mesenchymal transition (EMT) transcription factors, activates EMT, and promotes tumor metastasis. Here, we investigated the role and molecular mechanism of PER3 in regulating HIF-1α and metastasis in oral squamous cell carcinoma (OSCC) by using bioinformatics analyses and in vitro and in vivo experiments.
View Article and Find Full Text PDFHepatology
December 2024
Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
Objective: Chronic HBV infection (CHB) exhausts HBV-specific T cells, develops epigenetic imprints that impair immune responses, and limits the effectiveness of immune checkpoint inhibitor (ICI) monotherapy, such as αPD-L1. This study aimed to determine whether the DNA methyltransferase inhibitor decitabine (DAC) could reverse these epigenetic imprints and enhance ICI efficacy in restoring HBV-specific T cell responses.
Methods: We investigated HBV-specific T cell responses by 10-day in vitro stimulation of peripheral blood mononuclear cells (PBMCs) from patients with CHB.
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