Diallyl disulfide inhibits TNF induced CCL2 release through MAPK/ERK and NF-Kappa-B signaling. Academic Article uri icon

abstract

  • TNF receptors are constitutively overexpressed in tumor cells, correlating to sustain elevated NFB 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 TNF induced CCL2 production in MDA-MB-231 cells. In the current study, we explored the signaling pathways responsible for DADS suppressive effect on TNF mediated CCL2 release using PCR Arrays, RT-PCR and western blots. The data in this study show that TNF initiates a rise in NFB mRNA, which is not reversed by DADS. However, TNF induced heightened expression of IKK and phosphorylated ERK. The expression of these proteins corresponds to increased CCL2 release that can be attenuated by DADS. CCL2 induction by TNF 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 TNF invoked CCL2 production primarily through reduction of IKK and phosphorylated-ERK, thereby impairing MAPK/ERK, and NFB pathway signaling. Future research will be required to evaluate the effects of DADS on the function and expression of TNF surface receptors.

published proceedings

  • Cytokine

altmetric score

  • 0.25

author list (cited authors)

  • Bauer, D., Redmon, N., Mazzio, E., Taka, E., Reuben, J. S., Day, A., ... Darling-Reed, S.

citation count

  • 27

complete list of authors

  • Bauer, D||Redmon, N||Mazzio, E||Taka, E||Reuben, JS||Day, A||Sadrud-Din, S||Flores-Rozas, H||Soliman, KFA||Darling-Reed, S

publication date

  • January 2015