title: Honokiol induces cell cycle arrest and apoptosis via inhibiting class I histone deacetylases in acute myeloid leukemia.
abstract: 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.
authors.affiliation: Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical University, 2 FuXue Road, Wenzhou, 325000, China.
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Li
authors.forename: Hai-Ge
authors.initials: HG
authors.lastname: Ye
authors.forename: Chi-Qi
authors.initials: CQ
authors.lastname: Chen
authors.forename: Li-Hui
authors.initials: LH
authors.lastname: Yin
authors.forename: Jian-Bo
authors.initials: JB
authors.lastname: Wu
authors.forename: Li-Cai
authors.initials: LC
authors.lastname: He
authors.forename: Shen-Meng
authors.initials: SM
authors.lastname: Gao
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D055162:Biocatalysis / Q000187:drug effects; D001713:Biphenyl Compounds / Q000494:pharmacology*; D015153:Blotting, Western; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005260:Female; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology*; D008297:Male; D008819:Mice, Nude; D008875:Middle Aged; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D001713:Biphenyl Compounds; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004365:Drugs, Chinese Herbal; D006655:Histone Deacetylases; D017705:Lignans; D046988:Proteasome Endopeptidase Complex; D051028:bcl-2-Associated X Protein; C494826:BAX protein, human; C493956:CDKN1A protein, human; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols
keywords: BAX; HISTONE DEACETYLASES; HONOKIOL; P21/WAF1