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Diallyl disulfide inhibits TNFα induced CCL2 release through MAPK/ERK and NF-Kappa-B signaling

D Bauer1, N Redmon1, E Mazzio1

  • 1College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA.

Cytokine
|June 24, 2015
PubMed

Insights

Diallyl disulfide (DADS), a compound in garlic, reduces tumor-promoting CCL2 production by inhibiting key signaling pathways like IKKε and ERK. This suggests DADS

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Immunology

Background:

  • Tumor necrosis factor-alpha (TNFα) receptors are overexpressed in cancer cells, driving elevated NFκB and monocyte chemotactic protein-1 (MCP-1/CCL2) expression.
  • Elevated CCL2 promotes aggressive tumor behaviors including macrophage recruitment, proliferation, invasion, and angiogenesis.

Purpose of the Study:

  • To investigate the molecular mechanisms by which diallyl disulfide (DADS) suppresses TNFα-induced CCL2 production.
  • To identify the specific signaling pathways modulated by DADS in response to TNFα stimulation.

Main Methods:

  • Utilized PCR Arrays, RT-PCR, and Western blot analyses to examine gene and protein expression.
  • Assessed the impact of DADS and pathway-specific inhibitors (SB202190, U0126, SP 600125) on TNFα-mediated CCL2 release.

Main Results:

  • TNFα increased NFκB mRNA, IKKε, and phosphorylated ERK (p-ERK) expression, correlating with CCL2 release.
  • DADS attenuated TNFα-induced CCL2 production by reducing IKKε and p-ERK expression.
  • Inhibitors of p38 and MEK, but not JNK, lessened TNFα-induced CCL2, and these effects were suppressed by DADS.

Conclusions:

  • DADS downregulates TNFα-induced CCL2 production by inhibiting IKKε and phosphorylated-ERK signaling.
  • DADS impairs both MAPK/ERK and NFκB pathway signaling, offering a potential therapeutic strategy against aggressive tumors.
  • Further research is needed to explore DADS' effects on TNFα surface receptor function and expression.
Keywords:
Diallyl disulfideMap kinase bMonocyte chemoattractant protein 1Nuclear factor kappa bTumor necrosis factor alpha

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