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Article Open Access

Effect of apigenin on whole transcriptome profile of TNFα‑activated MDA‑MB‑468 triple negative breast cancer cells

  • Authors:
    • David Bauer
    • Elizabeth Mazzio
    • Aaron Hilliard
    • Ebenezer T. Oriaku
    • Karam F. A. Soliman
  • View Affiliations / Copyright

    Affiliations: Division of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA
    Copyright: © Bauer et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2123-2132
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    Published online on: January 22, 2020
       https://doi.org/10.3892/ol.2020.11327
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Abstract

The lack of hormone receptors in triple negative breast cancer (TNBC) is associated with the inefficacy of anti‑estrogen chemotherapies, leaving fewer options for patient treatment and higher mortality rates. Additionally, as with numerous types of inflammatory breast cancer, infiltration of tumor associated macrophages and other leukocyte sub‑populations within the tumor inevitably lead to aggressive, chemo‑resistant, metastatic and invasive types of cancer which escape immune surveillance. These processes are orchestrated by the release of potent cytokines, including TNFα, IL‑6 and CCL2 from the stroma, tumor and immune cells within the tumor microenvironment. The present study evaluated apigenin modulating effects on the pro‑inflammatory activating action of TNFα in TNBC MDA‑MB‑468 cells, derived from an African American woman. Initially, cell viability was determined to establish an optimal sub‑lethal dose of TNFα and apigenin in MDA‑MB‑468 cells. Subsequently, various treatments effects were evaluated using whole transcriptomic analysis of mRNA and long intergenic non‑coding RNA with Affymetrix HuGene‑2.1‑st human microarrays. Gene level differential expression analysis was conducted on 48,226 genes where TNFα caused significant upregulation of 53 transcripts and downregulation of 11 transcripts. The largest upward differential shift was for CCL2 [+61.86 fold change (FC); false discovery rate (FDR), P<0.0001]; which was down regulated by apigenin (to +10.71 FC vs. Control; FDR P‑value <0.001), equivalent to an 83% reduction. Several TNFα deferentially upregulated transcripts were reduced by apigenin, including CXCL10, C3, PGLYRP4, IL22RA2, KMO, IL7R, ROS1, CFB, IKBKe, SLITRK6 (a checkpoint target) and MMP13. Confirmation of CCL2 experimentally induced transcript alterations was corroborated at the protein level by ELISA assays. The high level of CCL2 transcript in the cell line was comparable to that in our previous studies in MDA‑MB‑231 cells. The differential effects of TNFα were corroborated by ELISA, where the data revealed a >10‑fold higher releasing rate of CCL2 in MDA‑MB‑468 cells compared with in MDA‑MB‑231 cells, both of which were attenuated by apigenin. The data obtained in the present study demonstrated a high level of CCL2 in MDA‑MB‑468 cells and a possible therapeutic role for apigenin in downregulating TNFα‑mediated processes in these TNBC cells.
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Copy and paste a formatted citation
Spandidos Publications style
Bauer D, Mazzio E, Hilliard A, Oriaku ET and Soliman KF: Effect of apigenin on whole transcriptome profile of TNFα‑activated MDA‑MB‑468 triple negative breast cancer cells. Oncol Lett 19: 2123-2132, 2020.
APA
Bauer, D., Mazzio, E., Hilliard, A., Oriaku, E.T., & Soliman, K.F. (2020). Effect of apigenin on whole transcriptome profile of TNFα‑activated MDA‑MB‑468 triple negative breast cancer cells. Oncology Letters, 19, 2123-2132. https://doi.org/10.3892/ol.2020.11327
MLA
Bauer, D., Mazzio, E., Hilliard, A., Oriaku, E. T., Soliman, K. F."Effect of apigenin on whole transcriptome profile of TNFα‑activated MDA‑MB‑468 triple negative breast cancer cells". Oncology Letters 19.3 (2020): 2123-2132.
Chicago
Bauer, D., Mazzio, E., Hilliard, A., Oriaku, E. T., Soliman, K. F."Effect of apigenin on whole transcriptome profile of TNFα‑activated MDA‑MB‑468 triple negative breast cancer cells". Oncology Letters 19, no. 3 (2020): 2123-2132. https://doi.org/10.3892/ol.2020.11327
Copy and paste a formatted citation
x
Spandidos Publications style
Bauer D, Mazzio E, Hilliard A, Oriaku ET and Soliman KF: Effect of apigenin on whole transcriptome profile of TNFα‑activated MDA‑MB‑468 triple negative breast cancer cells. Oncol Lett 19: 2123-2132, 2020.
APA
Bauer, D., Mazzio, E., Hilliard, A., Oriaku, E.T., & Soliman, K.F. (2020). Effect of apigenin on whole transcriptome profile of TNFα‑activated MDA‑MB‑468 triple negative breast cancer cells. Oncology Letters, 19, 2123-2132. https://doi.org/10.3892/ol.2020.11327
MLA
Bauer, D., Mazzio, E., Hilliard, A., Oriaku, E. T., Soliman, K. F."Effect of apigenin on whole transcriptome profile of TNFα‑activated MDA‑MB‑468 triple negative breast cancer cells". Oncology Letters 19.3 (2020): 2123-2132.
Chicago
Bauer, D., Mazzio, E., Hilliard, A., Oriaku, E. T., Soliman, K. F."Effect of apigenin on whole transcriptome profile of TNFα‑activated MDA‑MB‑468 triple negative breast cancer cells". Oncology Letters 19, no. 3 (2020): 2123-2132. https://doi.org/10.3892/ol.2020.11327
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