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Diallyl Disulfide Inhibits TNF‐alpha Induced CCL2 Release Through MAPK/ERK and NF‐Kappa‐B Signaling
Author(s) -
Bauer David,
Mazzio Elizabeth,
Soliman Karam,
DarlingReed Selina
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.lb148
Subject(s) - mapk/erk pathway , ccl2 , diallyl disulfide , tumor necrosis factor alpha , signal transduction , nf κb , chemistry , cancer research , chemotaxis , phosphorylation , microbiology and biotechnology , p38 mitogen activated protein kinases , monocyte , receptor , biology , chemokine , medicine , endocrinology , apoptosis , biochemistry
TNFα receptors are constitutively overexpressed in tumor cells, correlating to sustain elevated NFκB and monocyte chemotactic protein‐1 (MCP‐1 /CCL2) expression. The elevation of CCL2 evokes aggressive forms of malignant tumors marked by tumor associated macrophage (TAM) recruitment, cell proliferation, invasion and angiogenesis. Previously, we have shown that the organo‐sulfur compound diallyl disulfide (DADS) found in garlic ( Allium sativum) attenuates TNFα induced CCL2 production in MDA‐MB‐231 cells. In the current study, we explored the signaling responsible for DADS suppressive effect on TNFα mediated CCL2 release using Signaling Pathway NFκB RT² Profiler™ PCR Arrays, RT‐PCR and evaluation of MAPK/ERK signaling proteins. The data in this study show that TNFα initiates a rise in NFκB mRNA, which is not reversed by DADS. However, TNFα induced heightened expression of IKKe and phosphorylated ERK, corresponding to the rise of CCL2 release, both which were attenuated by DADS. CCL2 induction by TNFα was also lessened by inhibitors of p38 (SB202190) and MEK (U0126) but not JNK (SP 600125), all of which were suppressed by DADS. In conclusion, the obtained results indicate that DADS down regulates TNFα invoked CCL2 production primarily through reduction of IKKE and phosphorylated‐ERK, thereby impairing MAPK/ERK NFκB pathway signaling. Future research will be required to evaluate the effects of DADS on the function and expression of TNFα surface receptors.