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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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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
West Asia Organization for Cancer Prevention
2020
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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. |
format | Online Article Text |
id | pubmed-7779440 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | West Asia Organization for Cancer Prevention |
record_format | MEDLINE/PubMed |
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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