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

作者：Sun, Jing; Mu, Hongxiang; Yu, Jia; Li, Linwei; Yan, Hongxia; Li, Guoqing; Tan, Hui; Yang, Nanyang; Yang, Xiaoyan; Yi, Lan^*

来源：JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2019, 23(1): 194-204.

DOI：10.1111/jcmm.13904

• C/EBP alpha
• calreticulin
• diallyl disulphide
• differentiation
• human leukaemia cells

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-alpha (C/EBP alpha). We explored the expression of CRT and C/EBP alpha in clinical samples (20 healthy people and 19 acute myeloid leukaemia patients) and found that CRT and C/EBP alpha expressions were inversely correlated. DADS induction of differentiation of HL-60 cells resulted in down-regulated CRT expression and elevated C/EBP alpha 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 alpha in vivo. We also found that DADS-mediated down-regulation of CRT and up-regulation of C/EBP alpha involved enhancement of reactive oxidative species. RNA immunoprecipitation revealed that CRT bound C/EBP alpha mRNA, indicating its regulation of C/EBP alpha mRNA degradation by binding the UG-rich element in the 3 ' untranslated region of C/EBP alpha. In conclusion, the present study demonstrates the C/EBP alpha expression was correlated with CRT expression in vitro and in vivo and the molecular mechanism of DADS-induced leukaemic cell differentiation.

• 出版日期2019-1
• 单位南华大学