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

Abstract

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.

Diallyl Disulfide: A Bioactive Garlic Compound with Anticancer Potential

“…Furthermore, it was demonstrated that the DADS-mediated increased expression of C/EBPα and decreased expression of CRT expression resulted in an upregulation of reactive oxidant species. In an RNA immunoprecipitation experiment, CRT bound to C/EBPα mRNA, indicating that it controls C/EBPα mRNA degradation by conjugating with UGrich elements in the 3′ untranslated region ( Sun et al, 2019 ). The DADS-induced arrest of the G2/M phase in HL-60 cells may be linked to the activation of p38 MAP kinase.…”

High expression of calreticulin indicates poor prognosis and modulates cell migration and invasion via activating Stat3 in nasopharyngeal carcinoma

“…High expression of CALR is highly associated with invasion and metastasis, apoptosis resistance and poor prognosis in esophageal squamous cell carcinoma (ESCC), the capabilities of ESCC movement, invasion and resistant to apoptosis was significantly decreased after blocking endogenic expression of CALR24, 34. CALR expression was also higher in the more aggressive MDA-MB-231 cells compared with MCF-7 cells at both the mRNA and protein levels35, 36, siRNA-mediated knockdown of CRT expression significantly decreased invasiveness of DADS-treated HL-60 cells37, 38. In this study, we analyzed the clinical significance of CALR expression in NPC tissues.…”

From Natural Sources to Synthetic Derivatives: The Allyl Motif as a Powerful Tool for Fragment-Based Design in Cancer Treatment

“… 52 In addition, 5 has been shown to inhibit the growth of tumor tissue in immunodeficient mice injected with HL-60 cells. 53 As well as being able to inhibit the proliferation of, migration of, and invasion by leukemia cancer cells, 5 can arrest cells at the G0/G1 stage at low doses (8 μM). On the other hand, analysis of how 5 induced differentiation found four up-regulated proteins, including galactin-10, plectin 1, AUF1, and electron transfer flavoprotein α-subunit, and 14 down-regulated proteins, including DJ-1, cofilin 1, RhoGDP dissociation inhibitor 2 (RhoGDI2), calreticulin (CTR), and proliferating cell nuclear antigen (PCNA).…”