The short-term effect of histone deacetylase�inhibitors, chidamide and valproic acid, on�the�NF‑κB�pathway in multiple myeloma cells
| Autor: | Chenhuan Xiang, Rong Fu, Yangyang Wang, Qian Jing, Zhaoyun Liu, Yanqi Li, Fu Mi |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Time Factors Aminopyridines Apoptosis NF-κB Histones 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine NF-KappaB Inhibitor alpha chidamide Cell Line Tumor Chidamide Genetics Humans Phosphorylation histone deacetylase inhibitor Cell Proliferation Cell growth Valproic Acid NF-kappa B Acetylation Articles General Medicine Cell cycle Histone Deacetylase Inhibitors multiple myeloma IκBα 030104 developmental biology chemistry Cell culture 030220 oncology & carcinogenesis Benzamides Cancer research Histone deacetylase Signal Transduction |
| Zdroj: | International Journal of Molecular Medicine |
| ISSN: | 1791-244X 1107-3756 |
| DOI: | 10.3892/ijmm.2018.3963 |
| Popis: | Research regarding histone deacetylase (HDAC) inhibitors (HDACis) has garnered interest for the treatment of multiple myeloma (MM). In addition, the high expression of nuclear factor (NF)-κB in MM cells is considered an important factor in the occurrence and development of MM. The present study aimed to determine the short-term effects of HDACis, chidamide and valproic acid (VPA), on MM cells, their effects on NF-κB and the underlying mechanisms. The present study measured HDAC activity, and the proliferation and apoptosis of U266 and RPMI8226 MM cells following treatment with various concentrations of chidamide and VPA for 6 and 48 h. Western blotting was used to detect the expression levels of phosphorylated (p)-IκB kinase (IKK)α/β, NF-κB p65 and inhibitor of NF-κB (IκBα) in U266 and RPMI8226 cells at various time points following treatment with chidamide and VPA (0, 2, 4 and 6 h). The results revealed that chidamide and VPA had no significant effect on the HDAC activity, proliferation and apoptosis of cells at 6 h; however, cell HDAC activity and proliferation were inhibited, and apoptosis was induced at 48 h. Furthermore, the expression levels of IκBα were gradually increased over time, whereas the expression levels of NF-κB p65 gradually decreased. These findings indicated that long-term (48 h) treatment with the HDACis chidamide and VPA inhibited the proliferation and promoted the apoptosis of MM cells; however, these HDACis had little effect on cell proliferation and apoptosis in the short term (6 h). Notably, in the short term (2-6 h), hyperactivation of NF-κB was inhibited via the IκBα-NF-κB p65 pathway. These findings indicated that cell growth may be inhibited and drug susceptibility may be promoted by blocking the NF-κB pathway at an early stage, when HDACis are combined with other drugs in the treatment of MM. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|