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

摘要

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, style="fixed-case">DADS inhibited the growth of tumour tissue and decreased style="fixed-case">CRT levels and increased C/ style="fixed-case">EBPα in vivo. We also found that style="fixed-case">DADS‐mediated down‐regulation of style="fixed-case">CRT and up‐regulation of C/ style="fixed-case">EBPα involved enhancement of reactive oxidative species. style="fixed-case">RNA immunoprecipitation revealed that style="fixed-case">CRT bound C/ style="fixed-case">EBPα style="fixed-case">mRNA, indicating its regulation of C/ style="fixed-case">EBPα style="fixed-case">mRNA degradation by binding the style="fixed-case">UG‐rich element in the 3′ untranslated region of C/ style="fixed-case">EBPα. In conclusion, the present study demonstrates the C/ style="fixed-case">EBPα expression was correlated with style="fixed-case">CRT expression in vitro and in vivo and the molecular mechanism of style="fixed-case">DADS‐induced leukaemic cell differentiation.