Diallyl Disulfide Inhibits TNFα-induced CCL2 Release by MDA-MB-231 Cells

Monocyte chemotactic protein-1 (MCP-1/CCL2) is released by tumor tissues, serving as a potent chemokine enabling directional homing of mononuclear cells to tumor tissue, which subsequently differentiate into tumor-associated macrophages (TAMs) via TGF beta 1 signaling. TAMs readily invade tumor tissue and continue to synthesize pro-oncogenic proteins including tumor growth factors, matrix pro teases (metastasis), angiogenic factors (neovascularization) and CCL2. Substances, which can attenuate or block the initial release of CCL2 have been shown to prevent cancer-associated inflammative pro-oncogenic processes. In the current study, we investigated the effects of the organosulfur compound diallyl disulfide (DADS), a natural constituent of Allium sativum (garlic) on suppression of TNF alpha-induced release of CCL2 from triple-negative human breast tumor (MDA-MB-231) cells. Using an initial adipokine/chemokine protein panel microarray, the data show a predominant expression profile in resting/untreated MDA-MB-231 cells for sustained release of IL6, IL8, plasminogen Activator Inhibitor 1 and TIMP1/2. Treatment with TNF alpha (40 ng/ml) had no effect on many of these molecules, with a single major elevation in release of CCL2 (similar to 1,300-fold up-regulation). TNF alpha-induced CCL2 release was reversed by a sub-lethal concentration of DADS (100 mu M), evident in antibody based assays. These findings provide evidence to support another avenue of anticancer/chemopreventative properties attributable to garlic constituents through immunomodulation.