Mortality associated with breast cancer is attributable to aggressive metastasis, to which TNFalpha plays a central orchestrating role. TNFalpha acts on breast tumor TNF receptors evoking the release of chemotactic proteins (e.g. MCP-1/CCL2). These proteins direct inward infiltration/migration of tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), myeloid-derived suppressor cells (MDSCs), T-regulatory cells (Tregs), T helper IL-17-producing cells (Th17s), metastasis-associated macrophages (MAMs) and cancer-associated fibroblasts (CAFs). Tumor embedded infiltrates collectively enable immune evasion, tumor growth, angiogenesis, and metastasis. In the current study, we investigate the potential of apigenin, a known anti-inflammatory constituent of parsley, to downregulate TNFalpha mediated release of chemokines from human triple-negative cells (MDA-MB-231 cells). The results show that TNFalpha stimulation leads to large rise of CCL2, granulocyte macrophage colony-stimulating factor (GMCSF), IL-1alpha and IL-6, all suppressed by apigenin. While many aspects of the transcriptome for NFkB signaling were evaluated, the data show signaling patterns associated with CCL2 were blocked by apigenin and mediated through suppressed mRNA and protein synthesis of IKBKe. Moreover, the data show that the attenuation of CCL2 by apigenin in the presence TNFalpha paralleled the suppression of phosphorylated extracellular signal-regulated kinase 1 (ERK 1/ 2). In summary, the obtained findings suggest that there exists a TNFalpha evoked release of CCL2 and other LSP recruiting cytokines from human breast cancer cells, which can be attenuated by apigenin.

Author Info: (1) College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, Florida, United States of America. (2) College of Pharmacy and Pharmaceutical Sciences,

Author Info: (1) College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, Florida, United States of America. (2) College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, Florida, United States of America. (3) College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, Florida, United States of America. (4) College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, Florida, United States of America.