Honokiol induces cell cycle arrest and apoptosis via inhibiting class I histone deacetylases in acute myeloid leukemia
| Autor: | Hai-Ying, Li, Hai-Ge, Ye, Chi-Qi, Chen, Li-Hui, Yin, Jian-Bo, Wu, Li-Cai, He, Shen-Meng, Gao |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Adult
Cyclin-Dependent Kinase Inhibitor p21 Male Proteasome Endopeptidase Complex Blotting Western Mice Nude Apoptosis Histone Deacetylases Lignans Cell Line Tumor Tumor Cells Cultured Animals Humans Aged bcl-2-Associated X Protein Reverse Transcriptase Polymerase Chain Reaction Biphenyl Compounds Cell Cycle Checkpoints Middle Aged Xenograft Model Antitumor Assays Leukemia Myeloid Acute Disease Biocatalysis Female K562 Cells Drugs Chinese Herbal |
| Zdroj: | Journal of cellular biochemistry. 116(2) |
| ISSN: | 1097-4644 |
| Popis: | Honokiol, a constituent of Magnolia officinalis, has been reported to possess potent anti-cancer activity through targeting multiple signaling pathways in numerous malignancies including acute myeloid leukemia (AML). However, the underlying mechanisms remain to be defined. Here, we report that honokiol effectively decreased enzyme activity of histone deacetylases (HDACs) and reduced the protein expression of class I HDACs in leukemic cells. Moreover, treatment with proteasome inhibitor MG132 prevented honokiol-induced degradation of class I HDACs. Importantly, honokiol increased the levels of p21/waf1 and Bax via triggering acetylation of histone in the regions of p21/waf1 and Bax promoter. Honokiol induced apoptosis, decreased activity of HDACs, and significantly inhibited the clonogenic activity of hematopoietic progenitors in bone marrow mononuclear cells from patients with AML. However, honokiol did not decrease the activity of HDACs and induce apoptosis in normal hematopoietic progenitors from unbilicial cord blood. Finally, honokiol dramatically reduced tumorigenicity in a xenograft leukemia model. Collectively, our findings demonstrate that honokiol has anti-leukemia activity through inhibiting HDACs. Thus, being a relative non-toxic agent, honokiol may serve as a novel natural agent for cancer prevention and therapy in leukemia. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text