Open AccessDiallyl disulfide down‐regulates calreticulin and promotes C/ EBP α expression in differentiation of human leukaemia cells
Author(s) -
Sun Jing,
Mu Hongxiang,
Yu Jia,
Li Linwei,
Yan Hongxia,
Li Guoqing,
Tan Hui,
Yang Nanyang,
Yang Xiaoyan,
Yi Lan
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13904
Subject(s) - diallyl disulfide , calreticulin , in vivo , cellular differentiation , in vitro , microbiology and biotechnology , chemistry , chromatin immunoprecipitation , ccaat enhancer binding proteins , cancer research , cell growth , biology , gene expression , apoptosis , biochemistry , nuclear protein , transcription factor , gene , endoplasmic reticulum , promoter
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/ EBP α). We explored the expression of CRT and C/ EBP α in clinical samples (20 healthy people and 19 acute myeloid leukaemia patients) and found that CRT and C/ EBP α expressions were inversely correlated. DADS induction of differentiation of HL ‐60 cells resulted in down‐regulated CRT expression and elevated C/ EBP α 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/ EBP α in vivo. We also found that DADS ‐mediated down‐regulation of CRT and up‐regulation of C/ EBP α involved enhancement of reactive oxidative species. RNA immunoprecipitation revealed that CRT bound C/ EBP α mRNA , indicating its regulation of C/ EBP α mRNA degradation by binding the UG ‐rich element in the 3′ untranslated region of C/ EBP α. In conclusion, the present study demonstrates the C/ EBP α expression was correlated with CRT expression in vitro and in vivo and the molecular mechanism of DADS ‐induced leukaemic cell differentiation.