Garlic with DNA strands symbolizing leukaemia treatment.

Unlocking Leukaemia: How Garlic's Active Compound Could Revolutionize Treatment

"New Research Reveals Diallyl Disulfide's Promising Role in Differentiating Human Leukaemia Cells Through Calreticulin Regulation"


Acute myeloid leukaemia (AML) stands as a formidable and genetically diverse adversary, arising from the accumulation of somatic mutations within haematopoietic progenitor cells. Current strategies, encompassing surgery, radiation, and chemotherapy, offer relief but often fall short of eradicating the disease due to remaining tumour cells.

In light of these challenges, the induction of differentiation, a process that guides pre-malignant or malignant cells towards a more mature, benign state, has emerged as a promising therapeutic avenue. By selectively encouraging tumour cells to differentiate, scientists aim to eliminate these cells or reduce their malignant potential, paving the way for new treatments.

Amidst this pursuit, Diallyl disulfide (DADS), an active compound abundant in garlic, has garnered attention for its potential in combating cancer. Prior studies have illuminated DADS's ability to reduce the initiation of carcinogen-induced cancers and hinder the proliferation of various cancer cell types. Now, new research is diving deeper into how DADS interacts with human leukaemia cells, specifically exploring its influence on calreticulin (CRT), a protein involved in numerous cellular functions, and CCAAT enhancer binding protein-α (C/EBPα), crucial for normal neutrophil differentiation.

How DADS Impacts CRT and C/EBPα in Leukaemia Cells

Garlic with DNA strands symbolizing leukaemia treatment.

Researchers analysed clinical samples from healthy individuals and AML patients, they observed an inverse relationship between CRT and C/EBPα expression. High CRT levels were associated with low C/EBPα levels, and vice versa.

Further experiments with HL-60 leukaemia cells treated with DADS demonstrated that DADS treatment led to decreased CRT expression and increased C/EBPα expression. This was seen within combined immunodeficiency mice injected with HL-60 cells where DADS was found to inhibit the growth of tumour tissue, reduce CRT, and increase C/EBP in vivo.

  • Reactive Oxidative Species (ROS): DADS boosted ROS levels in leukaemia cells.
  • RNA Immunoprecipitation: CRT binds to C/EBPα mRNA, affecting its degradation and regulation in the 3' untranslated region of C/EBPα.
These findings suggest DADS could shift the balance of CRT and C/EBPα and trigger differentiation in the cells. Thus confirming that the molecular mechanism of DADS-induced leukaemic cell differentiation in vitro and in vivo correlated to C/EBPα expression.

The Future of Leukaemia Treatment with DADS

The findings may help to provide new solutions to leukaemia treatment by providing critical evidence of the molecular mechanisms of DADS-induced leukaemic cell differentiation, in which DADS induces CRT down-regulation and translocation through the ROS pathway, releasing the interaction between CRT and C/EBPα mRNA, promoting C/EBPα expression and inducing leukaemia cell differentiation.

About this Article -

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Everything You Need To Know

1

What is Diallyl disulfide (DADS) and why is it being studied in relation to leukaemia?

Diallyl disulfide, or DADS, is a compound found in garlic that is being researched for its potential to treat leukaemia. Research indicates DADS can influence the levels of specific proteins within leukaemia cells, potentially shifting them toward a more normal, less malignant state. This is significant because current leukaemia treatments sometimes fail to fully eliminate the disease, and DADS offers a novel approach by encouraging cells to differentiate into benign cells.

2

What is calreticulin (CRT) and why is it important in the context of leukaemia research?

Calreticulin, or CRT, is a protein that performs numerous functions within cells. In the context of leukaemia, CRT levels are being studied for their role in cell differentiation. Research suggests that decreasing CRT levels in leukaemia cells can help promote their differentiation into normal cells, reducing their malignant potential. This is important because high levels of CRT appear to be associated with lower levels of C/EBPα expression, which is crucial for normal neutrophil differentiation.

3

What is C/EBPα and what is its significance in leukaemia research?

C/EBPα, or CCAAT enhancer binding protein-α, is important for normal neutrophil differentiation. Studies show an inverse relationship between CRT and C/EBPα expression. The level of C/EBPα expression can be increased by decreasing CRT expression. Thus confirming that the molecular mechanism of DADS-induced leukaemic cell differentiation in vitro and in vivo correlated to C/EBPα expression.

4

What are Reactive Oxidative Species (ROS) and how do they relate to DADS and leukaemia cells?

Reactive Oxidative Species, or ROS, are highly reactive chemical molecules formed due to the effect of oxygen. DADS boosts ROS levels in leukaemia cells. This boost can lead to decreased CRT expression and increased C/EBPα expression, ultimately triggering differentiation in the cells.

5

What does RNA immunoprecipitation reveal about CRT and C/EBPα in leukaemia cells, and why is this significant?

RNA immunoprecipitation in this context is a technique used to show that CRT binds to C/EBPα mRNA, affecting its degradation and regulation in the 3' untranslated region of C/EBPα. This interaction is significant because it highlights how CRT levels can influence C/EBPα expression, which is crucial for cell differentiation. By understanding this binding mechanism, scientists can explore strategies to disrupt it and promote differentiation in leukaemia cells.

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