Diallyl disulfide down‐regulates calreticulin and promotes C/EBPα expression in differentiation of human leukaemia cells

Autor: Hongxia Yan, Hongxiang Mu, Xiaoyan Yang, Linwei Li, Hui Tan, Nanyang Yang, Jia Yu, Guoqing Li, Lan Yi, Jing Sun
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Untranslated region
Adult
Male
genetic structures
Adolescent
Cellular differentiation
Down-Regulation
HL-60 Cells
Mice
SCID
calreticulin
03 medical and health sciences
chemistry.chemical_compound
Young Adult
0302 clinical medicine
In vivo
Animals
Humans
Disulfides
3' Untranslated Regions
human leukaemia cells
Aged
Aged
80 and over
Messenger RNA
biology
Ccaat-enhancer-binding proteins
Diallyl disulfide
Cell Differentiation
Cell Biology
Original Articles
differentiation
Middle Aged
Molecular biology
Antineoplastic Agents
Phytogenic
Xenograft Model Antitumor Assays
In vitro
diallyl disulphide
Allyl Compounds
C/EBPα
Leukemia
Myeloid
Acute
030104 developmental biology
chemistry
030220 oncology & carcinogenesis
biology.protein
CCAAT-Enhancer-Binding Proteins
Molecular Medicine
Original Article
Female
Calreticulin
Zdroj: Journal of Cellular and Molecular Medicine
ISSN: 1582-4934
1582-1838
Popis: Diallyl disulfide (DADS), the main active component of the cancer fighting allyl sulfides found in garlic, has shown potential as a therapeutic agent in various cancers. Previous studies showed DADS induction of HL‐60 cell differentiation involves down‐regulation of calreticulin (CRT). Here, we investigated the mechanism of DADS‐induced differentiation of human leukaemia cells and the potential involvement of CRT and CCAAT enhancer binding protein‐α (C/EBPα). We explored the expression of CRT and C/EBPα in clinical samples (20 healthy people and 19 acute myeloid leukaemia patients) and found that CRT and C/EBPα expressions were inversely correlated. DADS induction of differentiation of HL‐60 cells resulted in down‐regulated CRT expression and elevated C/EBPα expression. In severe combined immunodeficiency mice injected with HL‐60 cells, DADS inhibited the growth of tumour tissue and decreased CRT levels and increased C/EBPα in vivo. We also found that DADS‐mediated down‐regulation of CRT and up‐regulation of C/EBPα involved enhancement of reactive oxidative species. RNA immunoprecipitation revealed that CRT bound C/EBPα mRNA, indicating its regulation of C/EBPα mRNA degradation by binding the UG‐rich element in the 3′ untranslated region of C/EBPα. In conclusion, the present study demonstrates the C/EBPα expression was correlated with CRT expression in vitro and in vivo and the molecular mechanism of DADS‐induced leukaemic cell differentiation.
Databáze: OpenAIRE
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