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Transcriptomic response of breast cancer cells to anacardic acid

David J Schultz1, Abirami Krishna2, Stephany L Vittitow2

  • 1Department of Biology, University of Louisville, Louisville, KY, USA.

Scientific Reports
|May 26, 2018
PubMed

Insights

Anacardic acid (AnAc) inhibits breast cancer cell proliferation by altering gene expression, impacting fatty acid synthesis and endoplasmic reticulum stress. This dietary agent shows potential for breast cancer prevention and treatment.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Anacardic acid (AnAc) is a potential dietary agent for breast cancer prevention and treatment.
  • AnAc inhibits proliferation in both estrogen receptor α (ERα)-positive and triple-negative breast cancer cells.
  • Previous studies identified AnAc-regulated microRNA (miRNA) transcriptomes.

Purpose of the Study:

  • To identify Anacardic acid-regulated messenger RNA (mRNA) and long non-coding RNA (lncRNA) transcript expression.
  • To characterize potential regulators of AnAc's anti-cancer activity.
  • To elucidate the molecular pathways modulated by AnAc in breast cancer cells.

Main Methods:

  • Treatment of MCF-7 and MDA-MB-231 breast cancer cells with purified AnAc 24:1n5 congener.
  • Next-generation transcriptomic sequencing (RNA-seq) for mRNA and lncRNA analysis.
  • Network analysis and pathway modeling to interpret gene expression changes.

Main Results:

  • AnAc modulated distinct mRNA and lncRNA transcriptomes in MCF-7 (80 genes) and MDA-MB-231 (886 genes) cells.
  • Six genes (SCD, INSIG1, TGM2, PDK4, GPR176, ZBT20) were commonly altered in both cell lines.
  • AnAc inhibited monounsaturated fatty acid biosynthesis and increased endoplasmic reticulum stress in MDA-MB-231 cells.
  • AnAc inhibited TNFα-induced NFκB reporter activity in MCF-7 cells.

Conclusions:

  • Anacardic acid affects key cellular processes including fatty acid biosynthesis and endoplasmic reticulum stress.
  • AnAc's anti-proliferative effects may involve the modulation of NFκB signaling.
  • Identified AnAc-regulated genes and pathways provide novel targets for breast cancer therapy.

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