Transcriptomic response of breast cancer cells to anacardic acid

David J. Schultz; Abirami Krishna; Stephany L. Vittitow; Negin Alizadeh-Rad; Penn Muluhngwi; Eric C. Rouchka; Carolyn M. Klinge

doi:10.1038/s41598-018-26429-x

Transcriptomic response of breast cancer cells to anacardic acid

David J. Schultz, Abirami Krishna, Stephany L. Vittitow, Negin Alizadeh-Rad, Penn Muluhngwi, Eric C. Rouchka, Carolyn M. Klinge

Research output: Contribution to journal › Article › peer-review

36 Scopus citations

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.

Original language	English (US)
Article number	8063
Journal	Scientific reports
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41598-018-26429-x
State	Published - Dec 1 2018
Externally published	Yes

Bibliographical note

Funding Information:
We thank Brandie N. Radde for performing the initial cell treatments and RNA isolation for RNA-seq. The research was supported in part by a pilot grant from the University of Louisville Center for Genetics and Molecular Medicine to C.M.K. and D.J.S.; and by an Internal Research Grant from the Office of the Executive Vice President for Research and Innovation of the University of Louisville to C.M.K.; E.C.R. and the KBRIN Bioinformatics core are supported by NIH/NIGMS grant P20 GM103436 (Nigel Cooper, PI); A.K. was supported by a NIH 5 T35 DK072923 (Carolyn M. Klinge, PI), S.L.V. was supported by the University of Louisville Summer Research Opportunity Program (SROP).

Publisher Copyright:
© 2018 The Author(s).

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title = "Transcriptomic response of breast cancer cells to anacardic acid",

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.",

author = "Schultz, {David J.} and Abirami Krishna and Vittitow, {Stephany L.} and Negin Alizadeh-Rad and Penn Muluhngwi and Rouchka, {Eric C.} and Klinge, {Carolyn M.}",

note = "Funding Information: We thank Brandie N. Radde for performing the initial cell treatments and RNA isolation for RNA-seq. The research was supported in part by a pilot grant from the University of Louisville Center for Genetics and Molecular Medicine to C.M.K. and D.J.S.; and by an Internal Research Grant from the Office of the Executive Vice President for Research and Innovation of the University of Louisville to C.M.K.; E.C.R. and the KBRIN Bioinformatics core are supported by NIH/NIGMS grant P20 GM103436 (Nigel Cooper, PI); A.K. was supported by a NIH 5 T35 DK072923 (Carolyn M. Klinge, PI), S.L.V. was supported by the University of Louisville Summer Research Opportunity Program (SROP). Publisher Copyright: {\textcopyright} 2018 The Author(s).",

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doi = "10.1038/s41598-018-26429-x",

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AU - Schultz, David J.

AU - Krishna, Abirami

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AU - Alizadeh-Rad, Negin

AU - Muluhngwi, Penn

AU - Rouchka, Eric C.

AU - Klinge, Carolyn M.

N1 - Funding Information: We thank Brandie N. Radde for performing the initial cell treatments and RNA isolation for RNA-seq. The research was supported in part by a pilot grant from the University of Louisville Center for Genetics and Molecular Medicine to C.M.K. and D.J.S.; and by an Internal Research Grant from the Office of the Executive Vice President for Research and Innovation of the University of Louisville to C.M.K.; E.C.R. and the KBRIN Bioinformatics core are supported by NIH/NIGMS grant P20 GM103436 (Nigel Cooper, PI); A.K. was supported by a NIH 5 T35 DK072923 (Carolyn M. Klinge, PI), S.L.V. was supported by the University of Louisville Summer Research Opportunity Program (SROP). Publisher Copyright: © 2018 The Author(s).

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

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Transcriptomic response of breast cancer cells to anacardic acid

Abstract

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