Premium
Apigenin Modulation of Whole Transcriptome Patterns of TNFα ‐ Induced Changes in Triple Negative Breast Cancer Cells, MDA‐MB‐231
Author(s) -
Bauer David,
Mazzio Elizabeth,
Soliman Karam F.
Publication year - 2017
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.31.1_supplement.809.3
Subject(s) - cancer research , tumor necrosis factor alpha , cytokine , chemokine , transcriptome , metastasis , biology , tumor microenvironment , apigenin , downregulation and upregulation , immunology , cxcl2 , angiogenesis , immune system , cancer , chemokine receptor , gene expression , gene , biochemistry , genetics , flavonoid , antioxidant
Mortality associated with breast cancer is primarily attributable to metastasis, of which TNFα plays a central orchestrating role. TNFα acts on the breast tumor TNF receptors evoking the release of chemotactic proteins (e.g. MCP‐1/CCL2). These proteins directs massive 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). These tumor embedded infiltrates collectively enable immune evasion, tumor growth, angiogenesis, and metastasis. In the current study, we investigated the potential of apigenin, a known anti‐inflammatory constituent of parsley, to alter the transcriptome patterns in TNFα treated triple negative breast cancer cells (MDA‐MB‐231). Whole genome expression profiling was carried out on Agilent Human 4 × 44 k arrays. The findings show TNFα mediated upregulation and apigenin downregulation of transcription patterns for the following genes: LAMC2, TMEM132A, TNFAIIP2, ICAM1, TLR2, IL32, IL4l1, CTSS, NEURL3, GBP5, IDO1, C3, EB13, ANO09, C1QTNF1‐AS1, BMPER, TNFSF15, IL 24, LINC00996, TRA2A, MAP3K5, LRG1, NEDD4l and PDA15. Pathway analysis shows the primary pathway involved in the effects of TNF were in the cytokine‐cytokine receptor interaction pathway, with sub‐categorical targets within the family of chemokines, TNF family and TGF‐Beta families. These data provide a general transcriptome pattern changes influence by TNFα, and modulated by apigenin in human breast cancer cells Support or Funding Information This research was supported by the National Institute of Minority Health and Health Disparities of the National Institutes of Health through Grant Number G12 MD007582 and Grant Number P20 MD006738.