Abstract
Anacardic acid (AnAc), a potential dietary agent for preventing and treating breast cancer, inhibited the proliferation of estrogen receptor α (ERα) positive MCF-7 and MDA-MB-231 triple negative breast cancer cells. To characterize potential regulators of AnAc action, MCF-7 and MDA-MB-231 cells were treated for 6 h with purified AnAc 24:1n5 congener followed by next generation transcriptomic sequencing (RNA-seq) and network analysis. We reported that AnAc-differentially regulated miRNA transcriptomes in each cell line and now identify AnAc-regulated changes in mRNA and lncRNA transcript expression. In MCF-7 cells, 80 AnAc-responsive genes were identified, including lncRNA MIR22HG. More AnAc-responsive genes (886) were identified in MDA-MB-231 cells. Only six genes were commonly altered by AnAc in both cell lines: SCD, INSIG1, and TGM2 were decreased and PDK4, GPR176, and ZBT20 were increased. Modeling of AnAc-induced gene changes suggests that AnAc inhibits monounsaturated fatty acid biosynthesis in both cell lines and increases endoplasmic reticulum stress in MDA-MB-231 cells. Since modeling of downregulated genes implicated NFκB in MCF-7, we confirmed that AnAc inhibited TNFα-induced NFκB reporter activity in MCF-7 cells. These data identify new targets and pathways that may account for AnAc’s anti-proliferative and pro-apoptotic activity.
Highlights
A number of plants produce anacardic acid (AnAc) which is a mixture of 6-alkylbenzoic acid congeners[1]
More genes were significantly changed in response to Anacardic acid (AnAc) in MDA-MB-231 cells vs MCF-7 cells (Fig. 1)
The major goal of this study was to identify the global effects of AnAc on the RNA transcriptome of two well-characterized cell lines representing luminal A, estrogen receptor α (ERα)+ (MCF-7) and triple negative breast cancer (TNBC) (MDA-MB-231) breast cancer
Summary
A number of plants produce anacardic acid (AnAc) which is a mixture of 6-alkylbenzoic acid congeners[1]. Transcriptome analysis using bioinformatics tools gives an overview of biological processes and pathways affected by a ‘drug’; providing new insights about the potential cellular targets and mechanisms of action of that ‘drug’ Identification of such targets using RNA-seq would be beneficial in identifying AnAc-regulated pathways and targets in both luminal A breast cancer and in TNBC which primarily affects premenopausal women with a predominance in women of African and Hispanic ancestry[4,5]. AnAc up- or down- regulated divergent and common mRNA transcripts in MCF-7 and MDA-MB-231 cells These results provide an overview of the processes and targets of AnAc in representative ERα+ and TNBC breast cancer cells in vitro. Comparison MCF-7 AnAc vs. control MDA-MB-231 AnAc vs. control All Cells AnAc vs. All Cells controlz All MCF-7 vs. All MDA-MB-231y
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