title: Diallyl disulfide inhibits TNFα-induced CCL2 release by MDA-MB-231 cells.
abstract: 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 TGFβ1 signaling. TAMs readily invade tumor tissue and continue to synthesize pro-oncogenic proteins including tumor growth factors, matrix proteases (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 TNFα-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 TNFα (40 ng/ml) had no effect on many of these molecules, with a single major elevation in release of CCL2 (~1,300-fold up-regulation). TNFα-induced CCL2 release was reversed by a sub-lethal concentration of DADS (100 μM), evident in antibody based assays. These findings provide evidence to support another avenue of anticancer/chemopreventative properties attributable to garlic constituents through immunomodulation.
authors.affiliation: College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, USA.
authors.forename: David
authors.initials: D
authors.lastname: Bauer
authors.affiliation: College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Mazzio
authors.affiliation: College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, USA.
authors.forename: Karam Fa
authors.initials: KF
authors.lastname: Soliman
authors.affiliation: College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, USA.
authors.forename: Equar
authors.initials: E
authors.lastname: Taka
authors.affiliation: College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, USA.
authors.forename: Ebenezer
authors.initials: E
authors.lastname: Oriaku
authors.affiliation: College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, USA.
authors.forename: Tracey
authors.initials: T
authors.lastname: Womble
authors.affiliation: College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL, USA selina.darling@famu.edu.
authors.forename: Selina
authors.initials: S
authors.lastname: Darling-Reed
mesh_terms: D054392:Adipokines / Q000378:metabolism; D000498:Allyl Compounds / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D018932:Chemokine CCL2 / Q000378:metabolism*; D004220:Disulfides / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005737:Garlic / Q000737:chemistry; D006801:Humans; D040081:Protein Array Analysis; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology
chemical_list: D054392:Adipokines; D000498:Allyl Compounds; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018932:Chemokine CCL2; D004220:Disulfides; D014409:Tumor Necrosis Factor-alpha; C028009:diallyl disulfide
keywords: Tumor-associated macrophages; diallyl disulfide; garlic constituents; monocyte chemotactic protein-1