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Integrative Bioinformatics Analysis Reveals Potential Target Genes and TNFα Signaling Inhibition by Brazilin in Metastatic Breast Cancer Cells

OBJECTIVE: Metastasis is the most significant cause of morbidity and mortality in breast cancer patients. Previously, a combination of brazilin and doxorubicin has been shown to inhibit metastasis in HER2-positive breast cancer cells. This present study used an integrative bioinformatics approach to...

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Autores principales: Hermawan, Adam, Putri, Herwandhani
Formato: Online Artículo Texto
Lenguaje:English
Publicado: West Asia Organization for Cancer Prevention 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779440/
https://www.ncbi.nlm.nih.gov/pubmed/32986377
http://dx.doi.org/10.31557/APJCP.2020.21.9.2751
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author Hermawan, Adam
Putri, Herwandhani
author_facet Hermawan, Adam
Putri, Herwandhani
author_sort Hermawan, Adam
collection PubMed
description OBJECTIVE: Metastasis is the most significant cause of morbidity and mortality in breast cancer patients. Previously, a combination of brazilin and doxorubicin has been shown to inhibit metastasis in HER2-positive breast cancer cells. This present study used an integrative bioinformatics approach to identify new targets and the molecular mechanism of brazilin in inhibiting metastasis in breast cancer. METHODS: Cytotoxicity and mRNA arrays data were retreived from the DTP website, whereas genes that regulate metastatic breast cancer cells were retreived from PubMed with keywords “breast cancer metastasis”. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and Drug association analysis were carried out by using WEB-based GEne SeT AnaLysis Toolkit (WebGestalt). Construction of protein-protein interaction (PPI) network analysis was performed by STRING-DB v11.0 and Cytoscape, respectively. The genetic alterations of the potential therapeutic target genes of brazilin (PB) were analyzed using cBioPortal. RESULTS: Analysis of cytotoxicity with the public database of COMPARE showed that brazilin exerts almost the same cytotoxicity in the NCI-60 cells panel showing by similar GI50 value, in which the lowest GI50 value was observed in MDA-MB 231, a metastatic breast cancer cells. KEGG enrichment indicated several pathways regulated by brazilin such as TNF signaling pathway, cellular senescence, and pathways in cancer. We found ten drugs that are associated with PB, including protein kinase inhibitors, TNFα inhibitors, enzyme inhibitors, and anti-inflammatory agents. CONCLUSION: In conclusion, this study identified eight PB, including MMP14, PTGS2, ADAM17, PTEN, CCL2, PIK3CB, MAP3K8, and CXCL3. In addition, brazilin possibly inhibits metastatic breast cancer through inhibition of TNFα signaling. The study results study need to be validated with in vitro and in vivo studies to strengthen scientific evidence of the use of brazilin in breast cancer metastasis inhibition.
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spelling pubmed-77794402021-01-08 Integrative Bioinformatics Analysis Reveals Potential Target Genes and TNFα Signaling Inhibition by Brazilin in Metastatic Breast Cancer Cells Hermawan, Adam Putri, Herwandhani Asian Pac J Cancer Prev Research Article OBJECTIVE: Metastasis is the most significant cause of morbidity and mortality in breast cancer patients. Previously, a combination of brazilin and doxorubicin has been shown to inhibit metastasis in HER2-positive breast cancer cells. This present study used an integrative bioinformatics approach to identify new targets and the molecular mechanism of brazilin in inhibiting metastasis in breast cancer. METHODS: Cytotoxicity and mRNA arrays data were retreived from the DTP website, whereas genes that regulate metastatic breast cancer cells were retreived from PubMed with keywords “breast cancer metastasis”. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and Drug association analysis were carried out by using WEB-based GEne SeT AnaLysis Toolkit (WebGestalt). Construction of protein-protein interaction (PPI) network analysis was performed by STRING-DB v11.0 and Cytoscape, respectively. The genetic alterations of the potential therapeutic target genes of brazilin (PB) were analyzed using cBioPortal. RESULTS: Analysis of cytotoxicity with the public database of COMPARE showed that brazilin exerts almost the same cytotoxicity in the NCI-60 cells panel showing by similar GI50 value, in which the lowest GI50 value was observed in MDA-MB 231, a metastatic breast cancer cells. KEGG enrichment indicated several pathways regulated by brazilin such as TNF signaling pathway, cellular senescence, and pathways in cancer. We found ten drugs that are associated with PB, including protein kinase inhibitors, TNFα inhibitors, enzyme inhibitors, and anti-inflammatory agents. CONCLUSION: In conclusion, this study identified eight PB, including MMP14, PTGS2, ADAM17, PTEN, CCL2, PIK3CB, MAP3K8, and CXCL3. In addition, brazilin possibly inhibits metastatic breast cancer through inhibition of TNFα signaling. The study results study need to be validated with in vitro and in vivo studies to strengthen scientific evidence of the use of brazilin in breast cancer metastasis inhibition. West Asia Organization for Cancer Prevention 2020-09 /pmc/articles/PMC7779440/ /pubmed/32986377 http://dx.doi.org/10.31557/APJCP.2020.21.9.2751 Text en This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Hermawan, Adam
Putri, Herwandhani
Integrative Bioinformatics Analysis Reveals Potential Target Genes and TNFα Signaling Inhibition by Brazilin in Metastatic Breast Cancer Cells
title Integrative Bioinformatics Analysis Reveals Potential Target Genes and TNFα Signaling Inhibition by Brazilin in Metastatic Breast Cancer Cells
title_full Integrative Bioinformatics Analysis Reveals Potential Target Genes and TNFα Signaling Inhibition by Brazilin in Metastatic Breast Cancer Cells
title_fullStr Integrative Bioinformatics Analysis Reveals Potential Target Genes and TNFα Signaling Inhibition by Brazilin in Metastatic Breast Cancer Cells
title_full_unstemmed Integrative Bioinformatics Analysis Reveals Potential Target Genes and TNFα Signaling Inhibition by Brazilin in Metastatic Breast Cancer Cells
title_short Integrative Bioinformatics Analysis Reveals Potential Target Genes and TNFα Signaling Inhibition by Brazilin in Metastatic Breast Cancer Cells
title_sort integrative bioinformatics analysis reveals potential target genes and tnfα signaling inhibition by brazilin in metastatic breast cancer cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779440/
https://www.ncbi.nlm.nih.gov/pubmed/32986377
http://dx.doi.org/10.31557/APJCP.2020.21.9.2751
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